Functional analysis of Ca3.2 T-type calcium channel mutations linked to childhood absence epilepsy.
OBJECTIVE
Childhood absence epilepsy (CAE) is an idiopathic form of seizure disorder that is believed to have a genetic basis.


METHODS
We examined the biophysical consequences of seven mutations in the Ca(v)3.2 T-type calcium channel gene linked to CAE.


RESULTS
Of the channel variants examined, one of the mutants, a replacement of glycine 848 in the domain II-S2 region with serine, resulted in significant slowing of the time courses of both activation and inactivation across a wide range of membrane potentials. These changes are consistent with increased channel activity in response to prolonged membrane depolarizations.


CONCLUSIONS
Taken together, these findings suggest that such little changes in channel gating may contribute to the etiology of CAE.
Peloquin
Jean B
JB
Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta.
Khosravani
Houman
H
Barr
Wendy
W
Bladen
Chris
C
Evans
Rhian
R
Mezeyova
Janette
J
Parker
David
D
Snutch
Terrance P
TP
McRory
John E
JE
Zamponi
Gerald W
GW
D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D004832:Epilepsy, Absence / Q000235:genetics* / Q000503:physiopathology; D005998:Glycine / Q000235:genetics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology; D008564:Membrane Potentials / Q000235:genetics; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D051381:Rats; D012694:Serine / Q000235:genetics
D020747:Calcium Channels, T-Type; D012694:Serine; D005998:Glycine