Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability
| Autor: | 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, JS |
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| Rok vydání: | 2014 |
| Předmět: |
1.1 Normal biological development and functioning
seizure Long-Term Potentiation Kcnb1tm1Dgen Action Potentials Convulsants Neurodegenerative Inbred C57BL Hippocampus Medical and Health Sciences Mice Shab Potassium Channels Underpinning research Seizures Flurothyl 2.1 Biological and endogenous factors Animals Aetiology Maze Learning Neurons Kcnb1 Epilepsy Neurology & Neurosurgery Kcnb1(tm1Dgen) Psychology and Cognitive Sciences Neurosciences Pilocarpine Biological Sciences Hyperactivity Brain Disorders Phenotype Neurological Gene Deletion |
| Zdroj: | Genes, brain, and behavior, vol 13, iss 4 Speca, DJ; Ogata, G; Mandikian, D; Bishop, HI; Wiler, SW; Eum, K; et al.(2014). Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability. Genes, Brain and Behavior, 13(4), 394-408. doi: 10.1111/gbb.12120. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/7j75t5d2 |
| Popis: | 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. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society. |
| Databáze: | OpenAIRE |
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