Specific Kinetic Alterations of Human CaV2.1 Calcium Channels Produced by Mutation S218L Causing Familial Hemiplegic Migraine and Delayed Cerebral Edema and Coma after Minor Head Trauma

Mutation S218L in the Ca(V)2.1 alpha(1) subunit of P/Q-type Ca(2+) channels produces a severe clinical phenotype in which typical attacks of familial hemiplegic migraine (FHM) triggered by minor head trauma are followed, after a lucid interval, by deep (even fatal) coma and long lasting severe cerebral edema. We investigated the functional consequences of this mutation on human Ca(V)2.1 channels expressed in human embryonic kidney 293 cells and in neurons from Ca(V)2.1 alpha(1)(-/-) mice by combining single channel and whole cell patch clamp recordings. Mutation S218L produced a shift to lower... Mehr ...