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Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain.

Publication ,  Journal Article
Grandl, J; Kim, SE; Uzzell, V; Bursulaya, B; Petrus, M; Bandell, M; Patapoutian, A
Published in: Nat Neurosci
June 2010

TRPV1 is the founding and best-studied member of the family of temperature-activated transient receptor potential ion channels (thermoTRPs). Voltage, chemicals and heat allosterically gate TRPV1. Molecular determinants of TRPV1 activation by capsaicin, allicin, acid, ammonia and voltage have been identified. However, the structures and mechanisms mediating TRPV1's pronounced temperature sensitivity remain unclear. Recent studies of the related channel TRPV3 identified residues in the pore region that are required for heat activation. We used both random and targeted mutagenesis screens of rat TRPV1 and identified point mutations in the outer pore region that specifically impair temperature activation. Single-channel analysis indicated that TRPV1 mutations disrupted heat sensitivity by ablating long channel openings, which are part of the temperature-gating pathway. We propose that sequential occupancy of short and long open states on activation provides a mechanism for enhancing temperature sensitivity. Our results suggest that the outer pore is important for the heat sensitivity of thermoTRPs.

Duke Scholars

Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

June 2010

Volume

13

Issue

6

Start / End Page

708 / 714

Location

United States

Related Subject Headings

  • Temperature
  • TRPV Cation Channels
  • Sequence Homology, Amino Acid
  • Sequence Alignment
  • Rats
  • Protein Structure, Tertiary
  • Protein Stability
  • Probability
  • Point Mutation
  • Patch-Clamp Techniques
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Grandl, J., Kim, S. E., Uzzell, V., Bursulaya, B., Petrus, M., Bandell, M., & Patapoutian, A. (2010). Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain. Nat Neurosci, 13(6), 708–714. https://doi.org/10.1038/nn.2552
Grandl, Jörg, Sung Eun Kim, Valerie Uzzell, Badry Bursulaya, Matt Petrus, Michael Bandell, and Ardem Patapoutian. “Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain.Nat Neurosci 13, no. 6 (June 2010): 708–14. https://doi.org/10.1038/nn.2552.
Grandl J, Kim SE, Uzzell V, Bursulaya B, Petrus M, Bandell M, et al. Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain. Nat Neurosci. 2010 Jun;13(6):708–14.
Grandl, Jörg, et al. “Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain.Nat Neurosci, vol. 13, no. 6, June 2010, pp. 708–14. Pubmed, doi:10.1038/nn.2552.
Grandl J, Kim SE, Uzzell V, Bursulaya B, Petrus M, Bandell M, Patapoutian A. Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain. Nat Neurosci. 2010 Jun;13(6):708–714.

Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

June 2010

Volume

13

Issue

6

Start / End Page

708 / 714

Location

United States

Related Subject Headings

  • Temperature
  • TRPV Cation Channels
  • Sequence Homology, Amino Acid
  • Sequence Alignment
  • Rats
  • Protein Structure, Tertiary
  • Protein Stability
  • Probability
  • Point Mutation
  • Patch-Clamp Techniques