演題詳細
Poster
てんかん、頭痛、めまい
Epilepsy, Headache, Vertigo
開催日 | 2014/9/11 |
---|---|
時間 | 11:00 - 12:00 |
会場 | Poster / Exhibition(Event Hall B) |
家族性片麻痺性片頭痛型CaV2.1チャネルの挙動異常の薬理学的補正
Pharmacological correction of gating defects in the voltage gated Ca(v)2.1 channel due to a Familial Hemiplegic Migraine Mutation
- P1-345
- 稲垣 彰 / Akira Inagaki:1 リー エイミー / Amy Lee:2
- 1:名古屋市立大学大学院医学研究科 / Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan 2:Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, US / Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, USA
Ca(v)2.1 is the channel that mediates P/Q type current which is widely observed in the neuronal cells, especially that in the brain. It plays pivotal roles in the neurotransmitter release and calcium spike formation as functioning as the major source of the Ca influx in the excitable cells triggered by the depolarization. Unlike L-type channels, pharmacological alteration of biophysical properties of Ca(v)2.1 has restrictions due to the scarcity of pharmacological agents. Here, we report that the 2',5'-di(tert-butyl)-1,4-benzohydroquinone (BHQ), modulates Ca(v)2.1 Ca2+ channels in ways that adverse defects in channel gating and synaptic transmission resulting from a familial hemiplegic migraine mutation (S218L). In transfected HEK293T cells, BHQ slows deactivation, inhibits voltage-dependent activation, and potentiates Ca2+-dependent facilitation of Ca(v)2.1 channels. Ca(v)2.1 channels with the S218L mutation show gating deficits including gain of function and reduced Ca2+-dependent facilitation, and BHQ helps offset these deficits. Our results reveal a mechanism by which a Ca(v)2.1 gating modifier can ameliorate defects associated with a disease-causing mutation in Ca(v)2.1.