Skip to main content
Journal cover image

Limbic epilepsy in transgenic mice carrying a Ca2+/calmodulin-dependent kinase II alpha-subunit mutation.

Publication ,  Journal Article
Butler, LS; Silva, AJ; Abeliovich, A; Watanabe, Y; Tonegawa, S; McNamara, JO
Published in: Proc Natl Acad Sci U S A
July 18, 1995

Multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMK) phosphorylates proteins pivotally involved in diverse neuronal processes and thereby coordinates cellular responses to external stimuli that regulate intracellular Ca2+ [Hanson, P. I. & Schulman, H. (1992) Annu. Rev. Biochem. 61, 559-664]. Despite extensive study, the impact of this enzyme on control of the excitability of neuron populations in the mammalian nervous system in situ is unknown. To address this question, we studied transgenic mice carrying a null mutation (-/-) for the alpha subunit of CaMK. In contrast to wild-type littermates, null mutants exhibit profound hyperexcitability, evident in epileptic seizures involving limbic structures including the hippocampus. No evidence of increased excitability was detected in mice carrying null mutations of the gamma isoform of protein kinase C, underscoring the specificity of the effect of CaMK. CaMK plays a powerful and previously underappreciated role in control of neuronal excitability in the mammalian nervous system. These insights have important implications for analyses of mechanisms of epilepsy and, perhaps, learning and memory.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

July 18, 1995

Volume

92

Issue

15

Start / End Page

6852 / 6855

Location

United States

Related Subject Headings

  • Seizures
  • Protein Kinase C
  • Mutation
  • Mice, Transgenic
  • Mice, Mutant Strains
  • Mice
  • Limbic System
  • Isoenzymes
  • Hippocampus
  • Epilepsy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Butler, L. S., Silva, A. J., Abeliovich, A., Watanabe, Y., Tonegawa, S., & McNamara, J. O. (1995). Limbic epilepsy in transgenic mice carrying a Ca2+/calmodulin-dependent kinase II alpha-subunit mutation. Proc Natl Acad Sci U S A, 92(15), 6852–6855. https://doi.org/10.1073/pnas.92.15.6852
Butler, L. S., A. J. Silva, A. Abeliovich, Y. Watanabe, S. Tonegawa, and J. O. McNamara. “Limbic epilepsy in transgenic mice carrying a Ca2+/calmodulin-dependent kinase II alpha-subunit mutation.Proc Natl Acad Sci U S A 92, no. 15 (July 18, 1995): 6852–55. https://doi.org/10.1073/pnas.92.15.6852.
Butler LS, Silva AJ, Abeliovich A, Watanabe Y, Tonegawa S, McNamara JO. Limbic epilepsy in transgenic mice carrying a Ca2+/calmodulin-dependent kinase II alpha-subunit mutation. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6852–5.
Butler, L. S., et al. “Limbic epilepsy in transgenic mice carrying a Ca2+/calmodulin-dependent kinase II alpha-subunit mutation.Proc Natl Acad Sci U S A, vol. 92, no. 15, July 1995, pp. 6852–55. Pubmed, doi:10.1073/pnas.92.15.6852.
Butler LS, Silva AJ, Abeliovich A, Watanabe Y, Tonegawa S, McNamara JO. Limbic epilepsy in transgenic mice carrying a Ca2+/calmodulin-dependent kinase II alpha-subunit mutation. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6852–6855.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

July 18, 1995

Volume

92

Issue

15

Start / End Page

6852 / 6855

Location

United States

Related Subject Headings

  • Seizures
  • Protein Kinase C
  • Mutation
  • Mice, Transgenic
  • Mice, Mutant Strains
  • Mice
  • Limbic System
  • Isoenzymes
  • Hippocampus
  • Epilepsy