Scholars@Duke
Ke Dong

Ke Dong

Professor in Biology
Biology
Office hours 9 am - 5 pm, Mon - Fri  

Selected Publications

A unique mechanism of transfluthrin action revealed by mapping its binding sites in the mosquito sodium channel.

Journal Article Insect biochemistry and molecular biology · December 2024 Pyrethroid insecticides exert their toxic action by prolonging the opening of insect voltage-gated sodium channels, resulting in the characteristic tail current during membrane repolarization in voltage clamp experiments. Permethrin (PMT) and deltamethrin ... Full text Cite

Role of DSC1 in Drosophila melanogaster synaptic activities in response to haedoxan A.

Journal Article Insect science · December 2023 Drosophila sodium channel 1 (DSC1) encodes a voltage-gated divalent cation channel that mediates neuronal excitability in insects. Previous research revealed that DSC1 knockout Drosophila melanogaster conferred different susceptibility to insecticides, whi ... Full text Cite

Bacterial pathogens deliver water- and solute-permeable channels to plant cells.

Journal Article Nature · September 2023 Many animal- and plant-pathogenic bacteria use a type III secretion system to deliver effector proteins into host cells1,2. Elucidation of how these effector proteins function in host cells is critical for understanding infectious diseases in animals and p ... Full text Open Access Link to item Cite

Insecticidal and Repellent Properties of Rapid-Acting Fluorine-Containing Compounds against Aedes aegypti Mosquitoes.

Journal Article ACS infectious diseases · July 2023 The development of safe and potent insecticides remains an integral part of a multifaceted strategy to effectively control human-disease-transmitting insect vectors. Incorporating fluorine can dramatically alter the physiochemical properties and bioavailab ... Full text Cite

Transfluthrin enhances odorant receptor-mediated spatial repellency in Aedes aegypti.

Journal Article Pesticide biochemistry and physiology · May 2023 Mosquito-borne diseases are an increasing global health challenge and vector-based interventions remain the most important methods for reducing the public health burden of most mosquito-borne diseases. Transfluthrin, a volatile pyrethroid insecticide, is u ... Full text Cite

Characterization of two kdr mutations at predicted pyrethroid receptor site 2 in the sodium channels of Aedes aegypti and Nilaparvata lugens.

Journal Article Insect biochemistry and molecular biology · September 2022 Pyrethroid insecticides prolong the opening of insect sodium channels by binding to two predicted pyrethroid receptor sites (PyR), PyR1 and PyR2. Many naturally-occurring sodium channel mutations that confer pyrethroid resistance (known as knockdown resist ... Full text Cite

Pyrethroids in an AlphaFold2 Model of the Insect Sodium Channel.

Journal Article Insects · August 2022 Pyrethroid insecticides stabilize the open state of insect sodium channels. Previous mutational, electrophysiological, and computational analyses led to the development of homology models predicting two pyrethroid receptor sites, PyR1 and PyR2. Many of the ... Full text Cite

Negative cross-resistance of a pyrethroid-resistant Drosophila mutant to Phryma leptostachya-derived haedoxan A.

Journal Article Insect science · June 2022 Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Mutations in sodium channel confer knockdown resistance (kdr) to pyrethroids in various arthropod pests. Haedoxan A (HA) is the major insecticidal component from Phryma leptos ... Full text Cite

Bioallethrin activates specific olfactory sensory neurons and elicits spatial repellency in Aedes aegypti.

Journal Article Pest management science · February 2022 BackgroundUse of pyrethroid insecticides is a pivotal strategy for mosquito control globally. Commonly known for their insecticidal activity by acting on voltage-gated sodium channels, pyrethroids, such as bioallethrin and transfluthrin, are used ... Full text Cite

Distinct roles of two RDL GABA receptors in fipronil action in the diamondback moth (Plutella xylostella).

Journal Article Insect science · December 2021 The phenylpyrazole insecticide fipronil blocks resistance to dieldrin (RDL) γ-aminobutyric acid (GABA) receptors in insects, thereby impairing inhibitory neurotransmission. Some insect species, such as the diamondback moth (Plutella xylostella), possess mo ... Full text Cite

Charge substitutions at the voltage-sensing module of domain III enhance actions of site-3 and site-4 toxins on an insect sodium channel.

Journal Article Insect biochemistry and molecular biology · October 2021 Scorpion α-toxins bind at the pharmacologically-defined site-3 on the sodium channel and inhibit channel inactivation by preventing the outward movement of the voltage sensor in domain IV (IVS4), whereas scorpion β-toxins bind at site-4 on the sodium chann ... Full text Cite

Behavioral and physiological responses of Drosophila melanogaster and D. suzukii to volatiles from plant essential oils.

Journal Article Pest management science · August 2021 Featured Publication BackgroundInsects rely on their sense of smell to locate food and hosts, find mates and select sites for laying eggs. Use of volatile compounds, such as essential oils (EOs), to repel insect pests and disrupt their olfaction-driven behaviors has g ... Full text Cite

Pyrethrins elicit olfactory response and spatial repellency in Aedes albopictus.

Journal Article Pest management science · August 2021 BackgroundPyrethrum from dry flowers of Chrysanthemum is a well-known botanical insecticide and repellent. Its insecticidal activity attributes to its six insecticidal esters, collectively known as pyrethrins. Pyrethrins and its synthetic analogs ... Full text Cite

Sodium channel activation underlies transfluthrin repellency in Aedes aegypti.

Journal Article PLoS neglected tropical diseases · July 2021 BackgroundVolatile pyrethroid insecticides, such as transfluthrin, have received increasing attention for their potent repellent activities in recent years for controlling human disease vectors. It has been long understood that pyrethroids kill in ... Full text Cite

Identification of multiple odorant receptors essential for pyrethrum repellency in Drosophila melanogaster.

Journal Article PLoS genetics · July 2021 Pyrethrum extract from dry flowers of Tanacetum cinerariifolium (formally Chrysanthemum cinerariifolium) has been used globally as a popular insect repellent against arthropod pests for thousands of years. However, the mechanistic basis of pyrethrum repell ... Full text Cite

Mapping the interaction surface of scorpion β-toxins with an insect sodium channel.

Journal Article The Biochemical journal · July 2021 The interaction of insect-selective scorpion depressant β-toxins (LqhIT2 and Lqh-dprIT3 from Leiurus quinquestriatus hebraeus) with the Blattella germanica sodium channel, BgNav1-1a, was investigated using site-directed mutagenesis, electrophysiological an ... Full text Cite

A dual-target molecular mechanism of pyrethrum repellency against mosquitoes.

Journal Article Nature communications · May 2021 Pyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents. While the molecular mechanisms of its insecticidal action are known, the molecular basis of pyrethrum repellency remains a mystery. In this ... Full text Cite

Three sodium channel mutations from Aedes albopictus confer resistance to Type I, but not Type II pyrethroids.

Journal Article Insect biochemistry and molecular biology · August 2020 Voltage-gated sodium channels are the major targets of several classes of insecticides, including pyrethroids. However, sensitivities of many insect pest species to pyrethroids have gradually decreased due to overuse in pest management programs. One major ... Full text Cite

Chronology of sodium channel mutations associated with pyrethroid resistance in Aedes aegypti.

Journal Article Archives of insect biochemistry and physiology · June 2020 Aedes aegypti is the primary mosquito vector of dengue, yellow fever, Zika and chikungunya. Current strategies to control Ae. aegypti rely heavily on insecticide interventions. Pyrethroids are a major class of insecticides used for mosquito control because ... Full text Cite

Distinct functional properties of sodium channel variants are associated with usage of alternative exons in Nilaparvata lugens.

Journal Article Insect biochemistry and molecular biology · March 2020 Voltage-gated sodium channels (Nav) are essential for electrical signaling in the nervous system. They are also the primary targets of several classes of insecticides including pyrethroids. There is only one sodium channel gene in most insect sp ... Full text Cite

Discovery of a Novel Series of Tricyclic Oxadiazine 4a-Methyl Esters Based on Indoxacarb as Potential Sodium Channel Blocker/Modulator Insecticides.

Journal Article Journal of agricultural and food chemistry · July 2019 Indoxacarb, a commercialized oxadiazine insecticide, nearly irreversibly blocks open/inactivated, but not resting sodium channels. The structure-activity relationships showed that the substituents at the position of the chiral atom in the oxadiazine ring a ... Full text Cite

Molecular evidence of sequential evolution of DDT- and pyrethroid-resistant sodium channel in Aedes aegypti.

Journal Article PLoS neglected tropical diseases · June 2019 BackgroundMultiple mutations in the voltage-gated sodium channel have been associated with knockdown resistance (kdr) to DDT and pyrethroid insecticides in a major human disease vector Aedes aegypti. One mutation, V1016G, confers sodium channel re ... Full text Open Access Cite

Action of six pyrethrins purified from the botanical insecticide pyrethrum on cockroach sodium channels expressed in Xenopus oocytes.

Journal Article Pesticide biochemistry and physiology · October 2018 Pyrethrin I, pyrethrin II, cinerin I, cinerin II, jasmolin I and jasmolin II are six closely related insecticidal active esters, known as pyrethrins, found in the pyrethrum extract from the dry flowers of Tanacetum cinerariifolium. The chemical structures ... Full text Cite

Mutational analysis of state-dependent contacts in the pore module of eukaryotic sodium channels.

Journal Article Archives of biochemistry and biophysics · August 2018 Voltage-gated sodium channels have residues that change or may change contacts upon gating. Contributions of individual contacts in stability of different states are incompletely understood. Pore-lining inner helices contain exceptionally conserved asparag ... Full text Cite

Block of Kir channels by flonicamid disrupts salivary and renal excretion of insect pests.

Journal Article Insect biochemistry and molecular biology · August 2018 Flonicamid is a selective insecticide for the control of sap-sucking insects; it exerts toxic effects by inhibiting insect feeding. However, its molecular target remains elusive. In this study, we functionally characterized NlKir1 channels of the brown pla ... Full text Cite

DSC1 channel-dependent developmental regulation of pyrethroid susceptibility in Drosophila melanogaster.

Journal Article Pesticide biochemistry and physiology · June 2018 Pyrethroid insecticides modify the gating of voltage-gated sodium channels, thus disrupting the function of the nervous system. In Drosophila melanogaster, para encodes a functional sodium channel. Drosophila Sodium Channel 1 (DSC1), although considered as ... Full text Cite

Comparative Antennal and Behavioral Responses of Summer and Winter Morph Drosophila suzukii (Diptera: Drosophilidae) to Ecologically Relevant Volatiles.

Journal Article Environmental entomology · June 2018 Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is a devastating global pest of berry crops and cherries. Little is understood about its biology during the winter in northern temperate regions, including potential resources that it may utilize duri ... Full text Cite

Neonicotinoid insecticide resistance among populations of Bemisia tabaci in the Mediterranean region of Turkey

Journal Article Bulletin of Insectology · January 1, 2018 The study was conducted to evaluate whether Bemisia tabaci (Gennadius) (MEAM1, formerly B biotype) populations in Turkey have developed resistance to neonicotinoid insecticides. We collected B. tabaci from vegetable and cotton growing areas in the Mediterr ... Cite

Molecular basis of selective resistance of the bumblebee BiNav1 sodium channel to tau-fluvalinate.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · December 2017 Insecticides are widely used to control pests in agriculture and insect vectors that transmit human diseases. However, these chemicals can have a negative effect on nontarget, beneficial organisms including bees. Discovery and deployment of selective insec ... Full text Cite

Molecular mechanism of knockdown resistance to pyrethroid insecticides

Journal Article Acta Horticulturae · July 25, 2017 Pyrethroid insecticides have been used extensively in controlling arthropod pests and disease vectors. They act on voltage-gated sodium channels, which are essential for the initiation and propagation of the action potential in neurons and other excitable ... Full text Cite

Introduction

Journal Article NeuroToxicology · May 1, 2017 Full text Cite

Alanine to valine substitutions in the pore helix IIIP1 and linker-helix IIIL45 confer cockroach sodium channel resistance to DDT and pyrethroids.

Journal Article Neurotoxicology · May 2017 Pyrethroid insecticides exert toxic effects by prolonging the opening of voltage-gated sodium channels. More than 20 sodium channel mutations from arthropod pests and disease vectors have been confirmed to confer pyrethroid resistance. These mutations have ... Full text Cite

Elucidation of pyrethroid and DDT receptor sites in the voltage-gated sodium channel.

Journal Article Neurotoxicology · May 2017 DDT and pyrethroid insecticides were among the earliest neurotoxins identified to act on voltage-gated sodium channels. In the 1960s, equipped with, at the time, new voltage-clamp techniques, Professor Narahashi and associates provided the initial evidence ... Full text Cite

Detection of a new pyrethroid resistance mutation (V410L) in the sodium channel of Aedes aegypti: a potential challenge for mosquito control.

Journal Article Scientific reports · April 2017 The yellow fever mosquito, Aedes aegypti, particularly in Neotropical regions, is the principal vector of dengue, yellow fever, Zika and Chikungunya viruses. Pyrethroids remain one of the most used insecticides to control Aedes mosquitoes, despite the deve ... Full text Cite

Mutations of two acidic residues at the cytoplasmic end of segment IIIS6 of an insect sodium channel have distinct effects on pyrethroid resistance.

Journal Article Insect biochemistry and molecular biology · March 2017 Mutations in sodium channels are known to confer knockdown resistance to pyrethroid insecticides, such as permethrin and cypermethrin, in various agricultural pests and disease vectors. Double mutations, D3i28V and E3i32G, were detect ... Full text Cite

Molecular Mechanism of Action and Selectivity of Sodium Ch annel Blocker Insecticides.

Journal Article Current medicinal chemistry · January 2017 Sodium channel blocker insecticides (SCBIs) are a relatively new class of insecticides that are represented by two commercially registered compounds, indoxacarb and metaflumizone. SCBIs, like pyrethroids and DDT, target voltage-gated sodium channels (VGSCs ... Full text Cite

Sodium Channel Mutations and Pyrethroid Resistance in Aedes aegypti.

Journal Article Insects · October 2016 Pyrethroid insecticides are widely used to control insect pests and human disease vectors. Voltage-gated sodium channels are the primary targets of pyrethroid insecticides. Mutations in the sodium channel have been shown to be responsible for pyrethroid re ... Full text Cite

The Receptor Site and Mechanism of Action of Sodium Channel Blocker Insecticides.

Journal Article The Journal of biological chemistry · September 2016 Sodium channels are excellent targets of both natural and synthetic insecticides with high insect selectivity. Indoxacarb, its active metabolite DCJW, and metaflumizone (MFZ) belong to a relatively new class of sodium channel blocker insecticides (SCBIs) w ... Full text Cite

Insight into the Mode of Action of Haedoxan A from Phryma leptostachya.

Journal Article Toxins · February 2016 Haedoxan A (HA) is a major active ingredient in the herbaceous perennial plant lopseed (Phryma leptostachya L.), which is used as a natural insecticide against insect pests in East Asia. Here, we report that HA delayed the decay rate of evoked excitatory j ... Full text Cite

Evidence for Dual Binding Sites for 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) in Insect Sodium Channels.

Journal Article The Journal of biological chemistry · February 2016 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), the first organochlorine insecticide, and pyrethroid insecticides are sodium channel agonists. Although the use of DDT is banned in most of the world due to its detrimental impact on the ecosystem, indoo ... Full text Cite

Two novel sodium channel mutations associated with resistance to indoxacarb and metaflumizone in the diamondback moth, Plutella xylostella.

Journal Article Insect science · February 2016 Indoxacarb and metaflumizone belong to a relatively new class of sodium channel blocker insecticides (SCBIs). Due to intensive use of indoxacarb, field-evolved indoxacarb resistance has been reported in several lepidopteran pests, including the diamondback ... Full text Cite

Molecular and functional characterization of a novel sodium channel TipE-like auxiliary subunit from the American cockroach Periplaneta americana.

Journal Article Insect biochemistry and molecular biology · November 2015 In Drosophila melanogaster, the functions of voltage-gated sodium (Nav) channels are modulated by TipE and its orthologs. Here, we describe a novel TipE homolog of the American cockroach, Periplaneta americana, called PaTipE. Like DmTipE, PaTipE mRNAs are ... Full text Cite

Mutations in the transmembrane helix S6 of domain IV confer cockroach sodium channel resistance to sodium channel blocker insecticides and local anesthetics.

Journal Article Insect biochemistry and molecular biology · November 2015 Indoxacarb and metaflumizone are two sodium channel blocker insecticides (SCBIs). They preferably bind to and trap sodium channels in the slow-inactivated non-conducting state, a mode of action similar to that of local anesthetics (LAs). Recently, two sodi ... Full text Cite

Rotational Symmetry of Two Pyrethroid Receptor Sites in the Mosquito Sodium Channel.

Journal Article Molecular pharmacology · August 2015 Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Although it is well known that specific mutations in insect sodium channels confer knockdown resistance (kdr) to pyrethroids, the atomic mechanisms of pyrethroid-sodium channe ... Full text Cite

The Drosophila Sodium Channel 1 (DSC1): The founding member of a new family of voltage-gated cation channels.

Journal Article Pesticide biochemistry and physiology · May 2015 It has been nearly three decades since the identification of the Drosophila Sodium Channel 1 (DSC1) gene from Drosophila melanogaster. The orthologs of the DSC1 gene have now been identified in other insect species including BSC1 from Blattella germanica. ... Full text Cite

Distinct modulating effects of TipE-homologs 2-4 on Drosophila sodium channel splice variants.

Journal Article Insect biochemistry and molecular biology · May 2015 The Drosophila melanogaster TipE protein is thought to be an insect sodium channel auxiliary subunit functionally analogous to the β subunits of mammalian sodium channels. Besides TipE, four TipE-homologous proteins (TEH1-4) have been identified. It has be ... Full text Cite

Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids.

Journal Article Neurotoxicology · March 2015 Voltage-gated sodium channels (Nav channels) are critical for electrical signaling in the nervous system and are the primary targets of the insecticides DDT and pyrethroids. In Drosophila melanogaster, besides the canonical Nav channel, Para (also called D ... Full text Cite

A mutation in the intracellular loop III/IV of mosquito sodium channel synergizes the effect of mutations in helix IIS6 on pyrethroid resistance.

Journal Article Molecular pharmacology · January 2015 Activation and inactivation of voltage-gated sodium channels are critical for proper electrical signaling in excitable cells. Pyrethroid insecticides promote activation and inhibit inactivation of sodium channels, resulting in prolonged opening of sodium c ... Full text Cite

Molecular description of scorpion toxin interaction with voltage–gated sodium channels

Chapter · January 1, 2015 Scorpion alpha and beta toxins interact with voltage-gated sodium channels (Navs) at two pharmacologically distinct sites. Alpha toxins bind at receptor site 3 and inhibit channel inactivation, whereas beta toxins bind at receptor site 4 and shi ... Full text Cite

Molecular biology of insect sodium channels and pyrethroid resistance.

Journal Article Insect biochemistry and molecular biology · July 2014 Voltage-gated sodium channels are essential for the initiation and propagation of the action potential in neurons and other excitable cells. Because of their critical roles in electrical signaling, sodium channels are targets of a variety of naturally occu ... Full text Cite

Sequence variations at I260 and A1731 contribute to persistent currents in Drosophila sodium channels.

Journal Article Neuroscience · May 2014 Tetrodotoxin-sensitive persistent sodium currents, INaP, that activate at subthreshold voltages, have been detected in numerous vertebrate and invertebrate neurons. These currents are believed to be critical for regulating neuronal excitability. However, t ... Full text Cite

Voltage-Gated Sodium Channels as Insecticide Targets.

Chapter · January 2014 Voltage-gated sodium channels are critical for the generation and propagation of action potentials. They are the primary target of several classes of insecticides, including DDT, pyrethroids and sodium channel blocker insecticides (SCBIs). DDT and pyrethro ... Full text Cite

A residue in the transmembrane segment 6 of domain I in insect and mammalian sodium channels regulate differential sensitivities to pyrethroid insecticides.

Journal Article Neurotoxicology · September 2013 Voltage-gated sodium channels are critical for electrical signaling in the nervous system. Pyrethroid insecticides exert their toxic action by modifying the gating of sodium channels. A valine to methionine mutation in the transmembrane segment 6 of domain ... Full text Cite

Molecular evidence for dual pyrethroid-receptor sites on a mosquito sodium channel.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · July 2013 Pyrethroid insecticides are widely used as one of the most effective control measures in the global fight against agricultural arthropod pests and mosquito-borne diseases, including malaria and dengue. They exert toxic effects by altering the function of v ... Full text Cite

Diversity and Convergence of Sodium Channel Mutations Involved in Resistance to Pyrethroids.

Journal Article Pesticide biochemistry and physiology · July 2013 Pyrethroid insecticides target voltage-gated sodium channels, which are critical for electrical signaling in the nervous system. The intensive use of pyrethroids in controlling arthropod pests and disease vectors has led to many instances of pyrethroid res ... Full text Cite

Differential effects of TipE and a TipE-homologous protein on modulation of gating properties of sodium channels from Drosophila melanogaster.

Journal Article PloS one · January 2013 β subunits of mammalian sodium channels play important roles in modulating the expression and gating of mammalian sodium channels. However, there are no orthologs of β subunits in insects. Instead, an unrelated protein, TipE in Drosophila melanogaster and ... Full text Cite

Intron retention in mRNA encoding ancillary subunit of insect voltage-gated sodium channel modulates channel expression, gating regulation and drug sensitivity.

Journal Article PloS one · January 2013 Insect voltage-gated sodium (Nav) channels are formed by a well-known pore-forming α-subunit encoded by para-like gene and ancillary subunits related to TipE from the mutation "temperature-induced-paralysis locus E." The role of these ancillary subunits in ... Full text Cite

Role of the DSC1 channel in regulating neuronal excitability in Drosophila melanogaster: extending nervous system stability under stress.

Journal Article PLoS genetics · January 2013 Voltage-gated ion channels are essential for electrical signaling in neurons and other excitable cells. Among them, voltage-gated sodium and calcium channels are four-domain proteins, and ion selectivity is strongly influenced by a ring of amino acids in t ... Full text Cite

Molecular characterization of DSC1 orthologs in invertebrate species.

Journal Article Insect biochemistry and molecular biology · May 2012 DSC1 and BSC1 are two founding members of a novel family of invertebrate voltage-gated cation channels with close structural and evolutionary relationships to voltage-gated sodium and calcium channels. In this study, we searched the published genome sequen ... Full text Cite

Evolutionary adaptation of the amino acid and codon usage of the mosquito sodium channel following insecticide selection in the field mosquitoes.

Journal Article PloS one · January 2012 Target site insensitivity resulting from point mutations within the voltage-gated sodium channel of the insect nervous system is known to be of primary importance in the development of resistance to pyrethroid insecticides. This study shifts current resear ... Full text Cite

Multiple mutations and mutation combinations in the sodium channel of permethrin resistant mosquitoes, Culex quinquefasciatus.

Journal Article Scientific reports · January 2012 A previous study identified 3 nonsynonymous and 6 synonymous mutations in the entire mosquito sodium channel of Culex quinquefasciatus, the prevalence of which were strongly correlated with levels of resistance and increased dramatically following insectic ... Full text Cite

Batrachotoxin, pyrethroids, and BTG 502 share overlapping binding sites on insect sodium channels.

Journal Article Molecular pharmacology · September 2011 Batrachotoxin (BTX), a steroidal alkaloid, and pyrethroid insecticides bind to distinct but allosterically coupled receptor sites on voltage-gated sodium channels and cause persistent channel activation. BTX presumably binds in the inner pore, whereas pyre ... Full text Cite

An important role of a pyrethroid-sensing residue F1519 in the action of the N-alkylamide insecticide BTG 502 on the cockroach sodium channel.

Journal Article Insect biochemistry and molecular biology · July 2011 Deltamethrin, a pyrethroid insecticide, and BTG 502, an alkylamide insecticide, target voltage-gated sodium channels. Deltamethrin binds to a unique receptor site and causes prolonged opening of sodium channels by inhibiting deactivation and inactivation. ... Full text Cite

Molecular characterization and functional expression of the DSC1 channel.

Journal Article Insect biochemistry and molecular biology · July 2011 Drosophila Sodium Channel 1 (DSC1) was predicted to encode a sodium channel based on a high sequence similarity with vertebrate and invertebrate sodium channel genes. However, BSC1, a DSC1 ortholog in Blattella germanica, was recently shown to encode a cat ... Full text Cite

Substitutions in the domain III voltage-sensing module enhance the sensitivity of an insect sodium channel to a scorpion beta-toxin.

Journal Article The Journal of biological chemistry · May 2011 Scorpion β-toxins bind to the extracellular regions of the voltage-sensing module of domain II and to the pore module of domain III in voltage-gated sodium channels and enhance channel activation by trapping and stabilizing the voltage sensor of domain II ... Full text Cite

Identification of new batrachotoxin-sensing residues in segment IIIS6 of the sodium channel.

Journal Article The Journal of biological chemistry · April 2011 Ion permeation through voltage-gated sodium channels is modulated by various drugs and toxins. The atomistic mechanisms of action of many toxins are poorly understood. A steroidal alkaloid batrachotoxin (BTX) causes persistent channel activation by inhibit ... Full text Cite

Drosophila as a model for epilepsy: bss is a gain-of-function mutation in the para sodium channel gene that leads to seizures.

Journal Article Genetics · February 2011 We report the identification of bang senseless (bss), a Drosophila melanogaster mutant exhibiting seizure-like behaviors, as an allele of the paralytic (para) voltage-gated Na(+) (Na(V)) channel gene. Mutants are more prone to seizure episodes than normal ... Full text Cite

A sodium channel mutation identified in Aedes aegypti selectively reduces cockroach sodium channel sensitivity to type I, but not type II pyrethroids.

Journal Article Insect biochemistry and molecular biology · January 2011 Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Numerous point mutations in sodium channel genes have been identified in pyrethroid-resistant insect species, and many have been confirmed to reduce or abolish sensitivity of ... Full text Cite

Analysis of the action of lidocaine on insect sodium channels.

Journal Article Insect biochemistry and molecular biology · January 2011 A new class of sodium channel blocker insecticides (SCBIs), which include indoxacarb, its active metabolite, DCJW, and metaflumizone, preferably block inactivated states of both insect and mammalian sodium channels in a manner similar to that by which loca ... Full text Cite

A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides.

Journal Article Toxicology and applied pharmacology · August 2010 Voltage-gated sodium channels are the primary target of pyrethroids, an important class of synthetic insecticides. Pyrethroids bind to a distinct receptor site on sodium channels and prolong the open state by inhibiting channel deactivation and inactivatio ... Full text Cite

Mechanism of action of sodium channel blocker insecticides (SCBIs) on insect sodium channels.

Journal Article Pesticide biochemistry and physiology · June 2010 Sodium channel blocker insecticides (SCBIs) are a relatively new class of insecticides, with a mechanism of action different from those of other classes of insecticides that target voltage-gated sodium channels. These compounds have no effect at hyperpolar ... Full text Cite

Functional expression of an arachnid sodium channel reveals residues responsible for tetrodotoxin resistance in invertebrate sodium channels.

Journal Article The Journal of biological chemistry · December 2009 Tetrodotoxin (TTX) is a potent blocker of voltage-gated sodium channels, but not all sodium channels are equally sensitive to inhibition by TTX. The molecular basis of differential TTX sensitivity of mammalian sodium channels has been largely elucidated. I ... Full text Cite

Impact of HLA in mother and child on disease progression of pediatric human immunodeficiency virus type 1 infection.

Journal Article Journal of virology · October 2009 A broad Gag-specific CD8(+) T-cell response is associated with effective control of adult human immunodeficiency virus (HIV) infection. The association of certain HLA class I molecules, such as HLA-B*57, -B*5801, and -B*8101, with immune control is linked ... Full text Cite

Role of the sixth transmembrane segment of domain IV of the cockroach sodium channel in the action of sodium channel blocker insecticides.

Journal Article Neurotoxicology · July 2009 Sodium channel blocker insecticides (SCBIs), such as indoxacarb and metaflumizone, are a new class of insecticides with a mechanism of action different from those of other insecticides that target sodium channels. SCBIs block sodium channels in a manner si ... Full text Cite

Identification of a cluster of residues in transmembrane segment 6 of domain III of the cockroach sodium channel essential for the action of pyrethroid insecticides.

Journal Article The Biochemical journal · April 2009 A phenylalanine residue (Phe1519) in the sixth transmembrane segment of domain III (IIIS6) of the cockroach BgNa(v) sodium channel is required for the binding and action of pyrethroids. However, whether or not other residues in IIIS6 participate in the act ... Full text Cite

Molecular characterization of a sodium channel gene from the Silkworm Bombyx mori.

Journal Article Insect biochemistry and molecular biology · February 2009 The voltage-gated sodium channel mediates the rapid rising phase of action potentials in almost all excitable cells and is a molecular target of a variety of neurotoxins including pyrethroid insecticides. Most studies have focused on the expression of sodi ... Full text Cite

Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides.

Journal Article Toxicology and applied pharmacology · January 2009 Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an alpha-cyano group at the phenylbenzyl alcohol position, which is lacking in ... Full text Cite

Use of non-mammalian alternative models for neurotoxicological study.

Journal Article Neurotoxicology · May 2008 The field of neurotoxicology needs to satisfy two opposing demands: the testing of a growing list of chemicals, and resource limitations and ethical concerns associated with testing using traditional mammalian species. National and international government ... Full text Cite

Molecular and functional characterization of voltage-gated sodium channel variants from Drosophila melanogaster.

Journal Article Insect biochemistry and molecular biology · May 2008 Extensive alternative splicing and RNA editing have been documented for the transcript of DmNa(V) (formerly para), the sole sodium channel gene in Drosophila melanogaster. However, the functional consequences of these post-transcriptional modifications are ... Full text Cite

The nicotinic acetylcholine receptor gene family of the silkworm, Bombyx mori.

Journal Article BMC genomics · September 2007 BackgroundNicotinic acetylcholine receptors (nAChRs) mediate fast synaptic cholinergic transmission in the insect central nervous system. The insect nAChR is the molecular target of a class of insecticides, neonicotinoids. Like mammalian nAChRs, i ... Full text Cite

Insect sodium channels and insecticide resistance.

Journal Article Invertebrate neuroscience : IN · March 2007 Voltage-gated sodium channels are essential for the generation and propagation of action potentials (i.e., electrical impulses) in excitable cells. Although most of our knowledge about sodium channels is derived from decades of studies of mammalian isoform ... Full text Cite

The differential preference of scorpion alpha-toxins for insect or mammalian sodium channels: implications for improved insect control.

Journal Article Toxicon : official journal of the International Society on Toxinology · March 2007 Receptor site-3 on voltage-gated sodium channels is targeted by a variety of structurally distinct toxins from scorpions, sea anemones, and spiders whose typical action is the inhibition of sodium current inactivation. This site interacts allosterically wi ... Full text Cite

The insecticidal potential of scorpion beta-toxins.

Journal Article Toxicon : official journal of the International Society on Toxinology · March 2007 Voltage-gated sodium channels are a major target for toxins and insecticides due to their central role in excitability, but due to the conservation of these channels in Animalia most insecticides do not distinguish between those of insects and mammals, the ... Full text Cite

Effect of a fluvalinate-resistance-associated sodium channel mutation from varroa mites on cockroach sodium channel sensitivity to fluvalinate, a pyrethroid insecticide.

Journal Article Insect biochemistry and molecular biology · November 2006 Fluvalinate is a pyrethroid insecticide that is widely used in the control of the varroa mite (Varroa destructor), an ecto-parasite of the honeybee. Previously we identified four fluvalinate-resistance-associated mutations in the sodium channel gene of the ... Full text Cite

Molecular basis of differential sensitivity of insect sodium channels to DCJW, a bioactive metabolite of the oxadiazine insecticide indoxacarb.

Journal Article Neurotoxicology · March 2006 Indoxacarb (DPX-JW062) was recently developed as a new oxadiazine insecticide with high insecticidal activity and low mammalian toxicity. Previous studies showed that indoxacarb and its bioactive metabolite, N-decarbomethoxyllated JW062 (DCJW), block insec ... Full text Cite

An alanine in segment 3 of domain III (IIIS3) of the cockroach sodium channel contributes to the low pyrethroid sensitivity of an alternative splice variant.

Journal Article Insect biochemistry and molecular biology · February 2006 In a previous study, we showed that two alternative exons (G1 and G2 encoding IIIS3-S4) were involved in the differential sensitivity of two cockroach sodium channel splice variants, BgNa(v)1-1 and BgNa(v)2-1 (previously called KD1 and KD2), to deltamethri ... Full text Cite

Identification of amino acid residues in the insect sodium channel critical for pyrethroid binding.

Journal Article Molecular pharmacology · February 2005 The voltage-gated sodium channel is the primary target site of pyrethroids, which constitute a major class of insecticides used worldwide. Pyrethroids prolong the opening of sodium channels by inhibiting deactivation and inactivation. Despite numerous atte ... Full text Cite

Persistent tetrodotoxin-sensitive sodium current resulting from U-to-C RNA editing of an insect sodium channel.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · August 2004 The persistent tetrodotoxin (TTX)-sensitive sodium current, detected in neurons of many regions of mammalian brains, is associated with many essential neuronal activities, including boosting of excitatory synaptic inputs, acceleration of firing rates, and ... Full text Cite

RNA editing generates tissue-specific sodium channels with distinct gating properties.

Journal Article The Journal of biological chemistry · July 2004 Sodium channels play an essential role in generating the action potential in eukaryotic cells, and their transcripts, especially those in insects, undergo extensive A-to-I RNA editing. The functional consequences of RNA editing of sodium channel transcript ... Full text Cite

A voltage-gated calcium-selective channel encoded by a sodium channel-like gene.

Journal Article Neuron · April 2004 BSC1, which was originally identified by its sequence similarity to voltage-gated Na(+) channels, encodes a functional voltage-gated cation channel whose properties differ significantly from Na(+) channels. BSC1 has slower kinetics of activation and inacti ... Full text Cite

Molecular characterization of an arachnid sodium channel gene from the varroa mite (Varroa destructor).

Journal Article Insect biochemistry and molecular biology · July 2003 Voltage-gated sodium channels are essential for the generation and propagation of action potentials in most excitable cells. They are the target sites of several classes of insecticides and acaricides. Isolation of full-length sodium channel cDNA is a crit ... Full text Cite

Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · July 2002 Alternative splicing is a major mechanism by which potassium and calcium channels increase functional diversity in animals. Extensive alternative splicing of the para sodium channel gene and developmental regulation of alternative splicing have been report ... Cite

Synergistic interaction between two cockroach sodium channel mutations and a tobacco budworm sodium channel mutation in reducing channel sensitivity to a pyrethroid insecticide.

Journal Article Insect biochemistry and molecular biology · April 2002 Pyrethroid insecticide resistance due to reduced nerve sensitivity, known as knockdown resistance (kdr or kdr-type), is linked to multiple point mutations in the para-homologous sodium channel genes. Previously we demonstrated that two mutations (E434K and ... Full text Cite

Novel sodium channel gene mutations in Blattella germanica reduce the sensitivity of expressed channels to deltamethrin.

Journal Article Insect biochemistry and molecular biology · April 2002 Pyrethroid insecticides alter the normal gating of voltage-gated sodium channels in the nervous system. Three sodium channel mutations (E434K, C764R, L993F) were recently identified in pyrethroid resistant German cockroach populations. In this report, we s ... Full text Cite

Association of novel mutations in a sodium channel gene with fluvalinate resistance in the mite, Varroa destructor

Journal Article Journal of Apicultural Research · January 1, 2002 Varroa (Varroa destructor) has recently become resistant to Apistan, a pyrethroid pesticide with tau-fluvalinate as its active ingredient. In many insect pests, resistance to pyrethroid insecticides is due to reduced target-site (sodium channel) sensitivit ... Full text Cite

Alternative splicing of the BSC1 gene generates tissue-specific isoforms in the German cockroach.

Journal Article Insect biochemistry and molecular biology · April 2001 Voltage-gated sodium channels are integral transmembrane proteins responsible for the rapidly-rising phase of action potentials in most excitable cells. In mammals, the functional diversity and wide distribution of sodium channel proteins in various tissue ... Full text Cite

Novel point mutations in the German cockroach para sodium channel gene are associated with knockdown resistance (kdr) to pyrethroid insecticides.

Journal Article Insect biochemistry and molecular biology · October 2000 Knockdown resistance (kdr) to pyrethroid insecticides has been attributed to point mutations in the para sodium channel gene in more than a half dozen insect pest species. In this study, we identified two novel para mutations in five highly resistant kdr-t ... Full text Cite

Mechanisms responsible for cypermethrin resistance in a strain of German cockroach, Blattella germanica

Journal Article Pesticide Biochemistry and Physiology · January 1, 2000 Cypermethrin resistance level and mechanisms responsible for the resistance were investigated in a strain (Aves) of German cockroach, Blattella germanica (L.), collected recently from a Gainesville, Florida residence. Topical bioassay data revealed that th ... Full text Cite

The knockdown resistance (kdr) mutation in pyrethroid-resistant German cockroaches

Journal Article Pesticide Biochemistry and Physiology · August 1, 1998 A point mutation in the para-homologous sodium channel gene has been shown to be associated with knockdown resistance (kdr) in several insect species including the German cockroach. In this study, we analyzed the genomic organization of the region where th ... Full text Cite

A single amino acid change in the para sodium channel protein is associated with knockdown-resistance (kdr) to pyrethroid insecticides in German cockroach.

Journal Article Insect biochemistry and molecular biology · February 1997 Previous genetic and pharmacological studies suggest that knockdown-resistance (kdr) to pyrethroid insecticides likely results from a mutation(s) in the para sodium channel gene. In this study, para sodium channel genes from an insecticide-susceptible Germ ... Full text Cite

Down-Regulation of Juvenile Hormone Esterase and Arylphorin Production in Heliothis virescens Larvae Parasitized by Microplitis croceipes

Journal Article Archives of Insect Biochemistry and Physiology · January 1, 1996 Previous studies have shown that juvenile hormone esterase (JHE) activity and arylphorin titer were dramatically reduced in the hemolymph of Heliothis virescens larvae parasitized by Microplitis croceipes. Similar changes were observed in calyx fluid-injec ... Full text Cite

kdr-Type resistance in insects with special reference to the German cockroach, Blattella germanica.

Journal Article Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology · October 1994 The phenomenon of knockdown resistance (kdr) was first noted in the housefly (Musca domestica), and has subsequently be found (i.e. kdr-type resistance) in several other insect pests including the German cockroach (Blattella germanica). This type of resist ... Full text Cite

Linkage of kdr-type resistance and the para-homologous sodium channel gene in German cockroaches (Blattella germanica).

Journal Article Insect biochemistry and molecular biology · July 1994 Pyrethroids are an important class of insecticides for controlling insect pests, including the German cockroach. Unfortunately, many insects have developed resistance to pyrethroids. One of the most important mechanisms of resistance is kdr (knockdown resi ... Full text Cite

[3H]Batrachotoxinin A-20-α-benzoate Binding in Synaptosomes from Susceptible and kdr-Type Resistant German Cockroaches, Blattella germanica (L.)

Journal Article Pesticide Biochemistry and Physiology · January 1, 1993 Synaptosomal binding of [3H]batrachotoxinin A-20-α-benzoate ([3H]BTX-B), a potent sodium channel toxin, was measured in kdr-type resistant (Ectiban-R) and susceptible (CSMA) German cockroaches. Previous studies indicated that the Ectiban-R strain was 8.7-f ... Full text Cite

Synergism of chlorpyrifos against the German cockroach, Blattella germanica.

Journal Article Medical and veterinary entomology · July 1992 Of fifteen compounds tested as synergists for chlorpyrifos against susceptible and resistant strains of Blattella germanica, the German cockroach, eleven were active against the resistant strain but only seven were synergistic against the susceptible strai ... Full text Cite

Neuropharmacology and genetics of kdr-type resistance in the German cockroach, Blattella germanica (L.)

Journal Article Pesticide Biochemistry and Physiology · January 1, 1991 The biochemistry and genetics of kdr-type resistance in the Ectiban-R strain of German cockroach were studied to provide information on the molecular basis of this resistance and to allow for more detailed comparison to the well-studied kdr mechanism in ho ... Full text Cite

Evaluation of the biochemical basis of insecticide selectivity between host and parasitoid species

Journal Article Environmental Entomology · December 1, 1990 Previously, we examined the effect of insecticides on four species of pteromalid parasitoids and their host, the house fly, Musca domestica L. Generally, the parasitoids are more susceptible to insecticides than the flies. In this study we examined the eff ... Full text Cite