Deletion of the K(V)1.1 potassium channel causes epilepsy in mice.
Mice lacking the voltage-gated potassium channel alpha subunit, K(V)1.1, display frequent spontaneous seizures throughout adult life. In hippocampal slices from homozygous K(V)1.1 null animals, intrinsic passive properties of CA3 pyramidal cells are normal. However, antidromic action potentials are recruited at lower thresholds in K(V)1.1 null slices. Furthermore, in a subset of slices, mossy fiber stimulation triggers synaptically mediated long-latency epileptiform burst discharges. These data indicate that loss of K(V)1.1 from its normal localization in axons and terminals of the CA3 region results in increased excitability in the CA3 recurrent axon collateral system, perhaps contributing to the limbic and tonic-clonic components of the observed epileptic phenotype. Axonal action potential conduction was altered as well in the sciatic nerve--a deficit potentially related to the pathophysiology of episodic ataxia/myokymia, a disease associated with missense mutations of the human K(V)1.1 gene.
Smart
S L
SL
The V.M. Bloedel Hearing Research Center, and the Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Washington, Seattle 98195, USA.
Lopantsev
V
V
Zhang
C L
CL
Robbins
C A
CA
Wang
H
H
Chiu
S Y
SY
Schwartzkroin
P A
PA
Messing
A
A
Tempel
B L
BL
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006624:Hippocampus / Q000502:physiology* / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D051662:Kv1.1 Potassium Channel; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009412:Nerve Fibers / Q000502:physiology; D015221:Potassium Channels / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017966:Pyramidal Cells / Q000502:physiology*; D015183:Restriction Mapping; D012584:Sciatic Nerve / Q000502:physiology; D012640:Seizures / Q000235:genetics / Q000503:physiopathology; D013569:Synapses / Q000502:physiology
C496946:KCNA1 protein, human; C496947:Kcna1 protein, mouse; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel