Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 279, Issue 11, Pages 9681-9684Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.C400006200
Keywords
-
Categories
Ask authors/readers for more resources
Childhood absence epilepsy (CAE) is a type of generalized epilepsy observed in 2 - 10% of epileptic children. In a recent study by Chen et al. ( Chen, Y., Lu, J., Pan, H., Zhang, Y., Wu, H., Xu, K., Liu, X., Jiang, Y., Bao, X., Yao, Z., Ding, K., Lo, W. H., Qiang, B., Chan, P., Shen, Y., and Wu, X. ( 2003) Ann. Neurol. 54, 239 - 243) 12 missense mutations were identified in the CACNA1H (Ca(v)3.2) gene in 14 of 118 patients with CAE but not in 230 control individuals. We have functionally characterized five of these mutations (F161L, E282K, C456S, V831M, and D1463N) using rat Ca(v)3.2 and whole-cell patch clamp recordings in transfected HEK293 cells. Two of the mutations, F161L and E282K, mediated an similar to10-mV hyperpolarizing shift in the half-activation potential. Mutation V831M caused a similar to 50% slowing of inactivation relative to control and shifted half-inactivation potential similar to 10 mV toward more depolarized potentials. Mean time to peak was significantly increased by mutation V831M but was unchanged for all others. No resolvable changes in the parameters of the IV relation or current kinetics were observed with the remaining mutations. The findings suggest that several of the Cav3.2 mutants allow for greater calcium influx during physiological activation and in the case of F161L and E282K can result in channel openings at more hyperpolarized ( close to resting) potentials. This may underlie the propensity for seizures in patients with CAE.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available