The effects of halothane on single human neuronal L-type calcium channels.
The effects of halothane on single human neuronal L-type calcium channels.
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氟烷对单个人神经元 L 型钙通道的影响。
DOI：
10.1097/00000539-199804000-00038
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发表时间：
1998
影响因子：
5.7
通讯作者：
Recio-Pinto,E
中科院分区：
文献类型：
--
作者：
Nikonorov,IM;Blanck,TJ;Recio-Pinto,E
采用细胞贴附式膜片钳技术，以Ba 2+为电荷载体，研究了氟烷对人神经细胞株SH SY 5 Y L型钙通道功能的影响。在多通道膜片钳中，氟烷降低了峰值和持续性Ba 2+电流，加速了失活速率，减慢了激活速率。单通道分析表明，氟烷（0.14-1.26 mM）增加了第一个通道开放的潜伏期时间，增加了非导电事件的寿命，增加了短暂的开放事件的比例，减少了两个开放人口的寿命，并增加了没有通道活动的电流痕迹的百分比。所有观察到的氟烷效应有助于氟烷诱导的宏观Ba 2+电流的减少。产生峰值Ba 2+电流50%降低的氟烷浓度（IC 50）为0.80 mM（28 [degree sign] C时约为1.9假设最小肺泡麻醉剂浓度[H-MAC]），持续性Ba 2+电流的IC 50为0.69 mM（约为1.7 H-MAC）。氟烷效应并不总是同时发生，Hill斜率为1.6，表明存在不止一个相互作用位点或不止一个L-型Ca 2+通道群体。氟烷主要通过稳定非传导状态如关闭状态（通道开放前后）和失活状态来降低人神经元细胞L型Ca 2+通道电流。结论：钙是神经元中的信号分子。我们用电子方法测定了氟烷对Ba 2+（一种Ca 2+替代物）向人神经元样细胞内运动的影响。Ba 2+通过L-型通道的进入被抑制。氟烷降低了通道开放的可能性，并提高了通道关闭和失活的速率。氟烷的这些作用可能与其麻醉作用有关。
We investigated halothane's effects on the function of L-type Ca 2+ channels in a human neuronal cell line, SH-SY5Y, by using the cell-attached patch voltage clamp configuration and Ba 2+ as the charge carrier. In multiple-channel patches, halothane decreased the peak and persistent Ba 2+ currents, accelerated the rate of inactivation, and slowed the rate of activation. Single-channel analysis showed that halothane (0.14-1.26 mM) increased the latency time for the first channel opening, increased the lifetime of nonconducting events, increased the proportion of short-lived open events, decreased the lifetime of the two open populations, and increased the percentage of current traces without channel activity. All of the observed halothane effects contribute to the halothane-induced decrease in macroscopic Ba 2+ currents. The halothane concentration producing 50% reduction (IC 50) of the peak Ba 2+ current was 0.80 mM (approximately 1.9 hypothetical minimum alveolar anesthetic concentration [H-MAC] at 28 [degree sign] C) and of the persistent Ba 2+ current was 0.69 mM (approximately 1.7 H-MAC). The halothane effects did not always occur together, and the Hill slope of 1.6 suggested the presence of more than one interaction site or of more than one population of L-type Ca 2+ channels. Halothane reduces L-type Ca 2+ channel currents in human neuronal cells primarily through the stabilization of nonconducting states such as closed (before and after channel opening) and inactivated states. Implications: Calcium is a signaling molecule in neurons. We measured the effect of halothane on Ba 2+(a Ca 2+ surrogate) movement into a human neuron-like cell electronically. Ba 2+ entry through the L-type channel was depressed. Halothane decreased the likelihood of the channel opening and enhanced the rate at which the channel closed and inactivated. These actions of halothane are probably related to its anesthetic action.