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三种不同门控模式下单一心脏钠通道的失活

Inactivation of single cardiac Na+ channels in three different gating modes.

作者信息

Böhle T, Steinbis M, Biskup C, Koopmann R, Benndorf K

机构信息

Department of Physiology, Friedrich-Schiller-University, D-07740 Jena, Germany.

出版信息

Biophys J. 1998 Oct;75(4):1740-8. doi: 10.1016/S0006-3495(98)77615-5.

DOI:10.1016/S0006-3495(98)77615-5
PMID:9746515
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1299845/
Abstract

In small cell-attached patches containing one and only one Na+ channel, inactivation was studied in three different gating modes, namely, the fast-inactivating F mode and the more slowly inactivating S mode and P mode with similar inactivation kinetics. In each of these modes, ensemble-averaged currents could be fitted with a Hodgkin-Huxley-type model with a single exponential for inactivation (tauh). tauh declined from 1.0 ms at -60 mV to 0.1 ms at 0 mV in the F mode, from 4.6 ms at -40 mV to 1.1 ms at 0 mV in the S mode, and from 4.5 ms at -40 mV to 0.8 ms at +20 mV in the P mode, respectively. The probability of non-empty traces (net), the mean number of openings per non-empty trace (op/tr), and the mean open probability per trace (popen) were evaluated at 4-ms test pulses. net inclined from 30% at -60 mV to 63% at 0 mV in the F mode, from 4% at -90 mV to 90% at 0 mV in the S mode, and from 2% at -60 mV to 79% at +20 mV in the P mode. op/tr declined from 1.4 at -60 mV to 1.1 at 0 mV in the F mode, from 4.0 at -60 mV to 1.2 at 0 mV in the S mode, and from 2.9 at -40 mV to 1.6 at +20 mV in the P mode. popen was bell-shaped with a maximum of 5% at -30 mV in the F mode, 48% at -50 mV in the S mode, and 16% at 0 mV in the P mode. It is concluded that 1) a switch between F and S modes may reflect a functional change of inactivation, 2) a switch between S and P modes may reflect a functional change of activation, 3) tauh is mainly determined by the latency until the first channel opening in the F mode and by the number of reopenings in the S and P modes, 4) at least in the S and P modes, inactivation is independent of pore opening, and 5) in the S mode, mainly open channels inactivate, and in the P mode, mainly closed channels inactivate.

摘要

在仅包含一个钠离子通道的小细胞贴附膜片中,研究了三种不同门控模式下的失活情况,即快速失活的F模式以及失活动力学相似但失活速度较慢的S模式和P模式。在每种模式下,总体平均电流都可以用具有单个失活指数(tauh)的霍奇金-赫胥黎型模型来拟合。在F模式下,tauh从-60 mV时的1.0毫秒降至0 mV时的0.1毫秒;在S模式下,从-40 mV时的4.6毫秒降至0 mV时的1.1毫秒;在P模式下,从-40 mV时的4.5毫秒降至+20 mV时的0.8毫秒。在4毫秒的测试脉冲下评估了非空轨迹的概率(net)、每个非空轨迹的平均开放次数(op/tr)以及每个轨迹的平均开放概率(popen)。在F模式下,net从-60 mV时的30%升至0 mV时的63%;在S模式下,从-90 mV时的4%升至0 mV时的90%;在P模式下,从-60 mV时的2%升至+20 mV时的79%。在F模式下,op/tr从-60 mV时的1.4降至0 mV时的1.1;在S模式下,从-60 mV时的4.0降至0 mV时的1.2;在P模式下,从-40 mV时的2.9降至+20 mV时的1.6。popen呈钟形,在F模式下-30 mV时最大为5%,在S模式下-50 mV时最大为48%,在P模式下0 mV时最大为16%。得出以下结论:1)F模式和S模式之间的转换可能反映了失活的功能变化;2)S模式和P模式之间的转换可能反映了激活的功能变化;3)tauh主要由F模式下直到第一个通道开放的延迟以及S模式和P模式下的重新开放次数决定;4)至少在S模式和P模式下,失活与孔开放无关;5)在S模式下,主要是开放通道失活,在P模式下,主要是关闭通道失活。

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本文引用的文献

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J Physiol. 1997 Apr 1;500 ( Pt 1)(Pt 1):85-94. doi: 10.1113/jphysiol.1997.sp022001.
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Impaired slow inactivation in mutant sodium channels.突变钠通道中缓慢失活受损。
Biophys J. 1996 Jul;71(1):227-36. doi: 10.1016/S0006-3495(96)79219-6.
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Slow inactivation of sodium channels: more than just a laboratory curiosity.钠通道的缓慢失活:不仅仅是实验室里的新奇现象。
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Voltage-dependent properties of three different gating modes in single cardiac Na+ channels.单个心脏钠通道三种不同门控模式的电压依赖性特性。
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