Dissociation of charge movement from calcium release and calcium current in skeletal myotubes by gabapentin.
Dissociation of charge movement from calcium release and calcium current in skeletal myotubes by gabapentin.
复制标题
加巴喷丁在骨骼肌管中从钙释放和钙电流中解离电荷运动。
DOI：
10.1152/ajpcell.00004.2002
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
García,Jesús
中科院分区：
文献类型：
--
作者：
Alden,KrisJ;García,Jesús
The skeletal muscle L-type calcium channel or dihydropyridine receptor (DHPR) plays an integral role in excitation-contraction (E-C) coupling. Its activation initiates three sequential events: charge movement (Qr), calcium release, and calcium current (ICa,L). This relationship suggests that changes in Qrmight affect release andICa,L. Here we studied the effect of gabapentin (GBP) on the three events generated by DHPRs in skeletal myotubes in culture. GBP specifically binds to the α2/δ1subunit of the brain and skeletal muscle DHPR. Myotubes were stimulated with a protocol that included a depolarizing prepulse to inactivate voltage-dependent proteins other than DHPRs. Gabapentin (50 μM) significantly increased Qrwhile decreasing the rate of rise of calcium transients. Gabapentin also reduced the maximum amplitude of theICa,L(as we previously reported) without modifying the kinetics of activation. Exposure of GBP-treated myotubes to 10 μM nifedipine prevented the increase of Qrpromoted by this drug, indicating that the extra charge recorded originated from DHPRs. Our data suggest that GBP dissociates the functions of the DHPR from the initial voltage-sensing step and implicates a role for the α2/δ1subunit in E-C coupling.
