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Functional Analysis of Ca v 3.2 T‐type Calcium Channel Mutations Linked to Childhood Absence Epilepsy
Author(s) -
Peloquin Jean B.,
Khosravani Houman,
Barr Wendy,
Bladen Chris,
Evans Rhian,
Mezeyova Janette,
Parker David,
Snutch Terrance P.,
McRory John E.,
Zamponi Gerald W.
Publication year - 2006
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2006.00482.x
Subject(s) - childhood absence epilepsy , epilepsy , calcium channel , gating , mutation , voltage dependent calcium channel , channelopathy , neuroscience , serine , calcium , t type calcium channel , genetics , chemistry , biology , medicine , gene , phosphorylation
Summary: Purpose: 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.