Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability

D. J. Speca, G. Ogata, D. Mandikian, H. I. Bishop, S. W. Wiler, K. Eum, H. Jürgen Wenzel, E. T. Doisy, L. Matt, K. L. Campi, M. S. Golub, J. M. Nerbonne, Johannes W Hell, B. C. Trainor, Jon T Sack, Philip A Schwartzkroin, James Trimmer

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1-/-) mice lacking this channel. Kv2.1-/- mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1-/- mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1-/- mice appear unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1-/- animals. Field recordings from hippocampal slices of Kv2.1-/- mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1-/- mice, long-term potentiation at the Schaffer collateral - CA1 synapse is decreased. Kv2.1-/- mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1-/- mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1-/- mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function. Kv2.1 mutant mice are strikingly hyperactive, susceptible to convulsant-induced seizures and defective in learning.

Original languageEnglish (US)
Pages (from-to)394-408
Number of pages15
JournalGenes, Brain and Behavior
Volume13
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Shab Potassium Channels
Delayed Rectifier Potassium Channels
Convulsants
Seizures
Neurons
Flurothyl
Pilocarpine
Bicuculline
Long-Term Potentiation
Synapses

Keywords

  • Hyperactivity
  • Kcnb1
  • Long-term potentiation
  • Seizure

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology
  • Medicine(all)

Cite this

Speca, D. J., Ogata, G., Mandikian, D., Bishop, H. I., Wiler, S. W., Eum, K., ... Trimmer, J. (2014). Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability. Genes, Brain and Behavior, 13(4), 394-408. https://doi.org/10.1111/gbb.12120

Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability. / Speca, D. J.; Ogata, G.; Mandikian, D.; Bishop, H. I.; Wiler, S. W.; Eum, K.; Wenzel, H. Jürgen; Doisy, E. T.; Matt, L.; Campi, K. L.; Golub, M. S.; Nerbonne, J. M.; Hell, Johannes W; Trainor, B. C.; Sack, Jon T; Schwartzkroin, Philip A; Trimmer, James.

In: Genes, Brain and Behavior, Vol. 13, No. 4, 2014, p. 394-408.

Research output: Contribution to journalArticle

Speca, DJ, Ogata, G, Mandikian, D, Bishop, HI, Wiler, SW, Eum, K, Wenzel, HJ, Doisy, ET, Matt, L, Campi, KL, Golub, MS, Nerbonne, JM, Hell, JW, Trainor, BC, Sack, JT, Schwartzkroin, PA & Trimmer, J 2014, 'Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability', Genes, Brain and Behavior, vol. 13, no. 4, pp. 394-408. https://doi.org/10.1111/gbb.12120
Speca, D. J. ; Ogata, G. ; Mandikian, D. ; Bishop, H. I. ; Wiler, S. W. ; Eum, K. ; Wenzel, H. Jürgen ; Doisy, E. T. ; Matt, L. ; Campi, K. L. ; Golub, M. S. ; Nerbonne, J. M. ; Hell, Johannes W ; Trainor, B. C. ; Sack, Jon T ; Schwartzkroin, Philip A ; Trimmer, James. / Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability. In: Genes, Brain and Behavior. 2014 ; Vol. 13, No. 4. pp. 394-408.
@article{f01a09db54dc4a7e8375c5ac3ce27c67,
title = "Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability",
abstract = "The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1-/-) mice lacking this channel. Kv2.1-/- mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1-/- mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1-/- mice appear unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1-/- animals. Field recordings from hippocampal slices of Kv2.1-/- mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1-/- mice, long-term potentiation at the Schaffer collateral - CA1 synapse is decreased. Kv2.1-/- mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1-/- mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1-/- mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function. Kv2.1 mutant mice are strikingly hyperactive, susceptible to convulsant-induced seizures and defective in learning.",
keywords = "Hyperactivity, Kcnb1, Long-term potentiation, Seizure",
author = "Speca, {D. J.} and G. Ogata and D. Mandikian and Bishop, {H. I.} and Wiler, {S. W.} and K. Eum and Wenzel, {H. J{\"u}rgen} and Doisy, {E. T.} and L. Matt and Campi, {K. L.} and Golub, {M. S.} and Nerbonne, {J. M.} and Hell, {Johannes W} and Trainor, {B. C.} and Sack, {Jon T} and Schwartzkroin, {Philip A} and James Trimmer",
year = "2014",
doi = "10.1111/gbb.12120",
language = "English (US)",
volume = "13",
pages = "394--408",
journal = "Genes, Brain and Behavior",
issn = "1601-1848",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability

AU - Speca, D. J.

AU - Ogata, G.

AU - Mandikian, D.

AU - Bishop, H. I.

AU - Wiler, S. W.

AU - Eum, K.

AU - Wenzel, H. Jürgen

AU - Doisy, E. T.

AU - Matt, L.

AU - Campi, K. L.

AU - Golub, M. S.

AU - Nerbonne, J. M.

AU - Hell, Johannes W

AU - Trainor, B. C.

AU - Sack, Jon T

AU - Schwartzkroin, Philip A

AU - Trimmer, James

PY - 2014

Y1 - 2014

N2 - The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1-/-) mice lacking this channel. Kv2.1-/- mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1-/- mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1-/- mice appear unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1-/- animals. Field recordings from hippocampal slices of Kv2.1-/- mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1-/- mice, long-term potentiation at the Schaffer collateral - CA1 synapse is decreased. Kv2.1-/- mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1-/- mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1-/- mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function. Kv2.1 mutant mice are strikingly hyperactive, susceptible to convulsant-induced seizures and defective in learning.

AB - The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1-/-) mice lacking this channel. Kv2.1-/- mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1-/- mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1-/- mice appear unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1-/- animals. Field recordings from hippocampal slices of Kv2.1-/- mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1-/- mice, long-term potentiation at the Schaffer collateral - CA1 synapse is decreased. Kv2.1-/- mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1-/- mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1-/- mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function. Kv2.1 mutant mice are strikingly hyperactive, susceptible to convulsant-induced seizures and defective in learning.

KW - Hyperactivity

KW - Kcnb1

KW - Long-term potentiation

KW - Seizure

UR - http://www.scopus.com/inward/record.url?scp=84897962170&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897962170&partnerID=8YFLogxK

U2 - 10.1111/gbb.12120

DO - 10.1111/gbb.12120

M3 - Article

VL - 13

SP - 394

EP - 408

JO - Genes, Brain and Behavior

JF - Genes, Brain and Behavior

SN - 1601-1848

IS - 4

ER -