Inhibition of M-current in cultured rat superior cervical ganglia by linopirdine: Mechanism of action studies
Inhibition of M-current in cultured rat superior cervical ganglia by linopirdine: Mechanism of action studies
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DOI：
10.1016/s0028-3908(97)00155-x
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发表时间：
1997-11-01
影响因子：
4.7
通讯作者：
Brown, BS
中科院分区：
文献类型：
--
作者：
Costa, AMN;Brown, BS
采用全细胞膜片钳技术，在培养的大鼠上级颈交感神经节上研究了利诺吡啶阻断M电流的机制。比较了细胞内信号转导通路的调节剂对毒蕈碱或利诺吡啶诱导的M电流抑制的影响。胞内添加GDP-β-S（500 μ M）减弱了毒蕈碱（1 μ M）对M-电流的阻断，但对利诺吡啶（10 μ M）没有影响。GTP-gamma-S（100 μ M）的细胞内透析增强并延长了毒蕈碱诱导的M-电流抑制，但对利诺吡啶的活性没有影响。细胞内BAPTA（20 mM）也抑制毒蕈碱的影响，而不影响那些利诺吡啶。细胞内应用利诺吡啶没有影响基础M-电流振幅或利诺吡啶阻断M-电流的能力时，细胞外给药。这些结果表明，M-电流抑制利诺吡啶是不太可能的G-蛋白介导的或钙介导的或涉及细胞内的作用位点，因此，与M-通道从其细胞外侧的直接阻断一致。(C)1998爱思唯尔科技有限公司版权所有。
The mechanism involved in the blockade of M-current by linopirdine was studied in cultured rat superior cervical sympathetic ganglia using whole-cell patch clamp recording. The effects of modulators of intracellular signal transduction pathways on muscarine-or linopirdine-induced inhibition of M-current were compared. Intracellular addition of GDP-beta-S (500 mu M) attenuated M-current block by muscarine (1 mu M) but not that of linopirdine (10 mu M). Intracellular dialysis of GTP-gamma-S (100 mu M) enhanced and prolonged muscarine-induced inhibition of M-current but had no effect on the activity of linopirdine. Intracellular BAPTA (20 mM) also inhibited the effects of muscarine without affecting those of linopirdine. Intracellular application of linopirdine had no effect on either basal M-current amplitude or the ability of linopirdine to block M-current when administered extracellularly. These results indicate that M-current inhibition by linopirdine is unlikely to be either G-protein-mediated or calcium-mediated or to involve an intracellular site of action and are, therefore, consistent with a direct block of the M-channel from its extracellular side. (C) 1998 Elsevier Science Ltd. All rights reserved.