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心脏钠电流以及单个心脏钠通道的失活、重新开放和等待特性。

Cardiac Na currents and the inactivating, reopening, and waiting properties of single cardiac Na channels.

作者信息

Kunze D L, Lacerda A E, Wilson D L, Brown A M

出版信息

J Gen Physiol. 1985 Nov;86(5):691-719. doi: 10.1085/jgp.86.5.691.

DOI:10.1085/jgp.86.5.691
PMID:2415670
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2228812/
Abstract

Tetrodotoxin (TTX)-sensitive Na currents were examined in single dissociated ventricular myocytes from neonatal rats. Single channel and whole cell currents were measured using the patch-clamp method. The channel density was calculated as 2/micron 2, which agreed with our usual finding of four channels per membrane patch. At 20 degrees C, the single channel conductance was 20 pS. The open time distributions were fit by a single-exponential function with a mean open time of approximately 1.0 ms at membrane potentials from -60 to -40 mV. Averaged single channel and whole cell currents were similar when scaled and showed both fast and slow rates of inactivation. The inactivation and activation gating shifted quickly to hyperpolarized potentials for channels in cell-attached as well as excised patches, whereas a much slower shift occurred in whole cells. Slowly inactivating currents were present in both whole cell and single channel current measurements at potentials as positive as -40 mV. In whole cell measurements, the potential range could be extended, and slow inactivation was present at potentials as positive as -10 mV. The curves relating steady state activation and inactivation to membrane potential had very little overlap, and slow inactivation occurred at potentials that were positive to the overlap. Slow inactivation is in this way distinguishable from the overlap or window current, and the slowly inactivating current may contribute to the plateau of the rat cardiac action potential. On rare occasions, a second set of Na channels having a smaller unit conductance and briefer duration was observed. However, a separate set of threshold channels, as described by Gilly and Armstrong (1984. Nature [Lond.]. 309:448), was not found. For the commonly observed Na channels, the number of openings in some samples far exceeded the number of channels per patch and the latencies to first opening or waiting times were not sufficiently dispersed to account for the slowly inactivating currents: the slow inactivation was produced by channel reopening. A general model was developed to predict the number of openings in each sample. Models in which the number of openings per sample was due to a dispersion of waiting times combined with a rapid transition from an open to an absorbing inactivated state were unsatisfactory and a model that was more consistent with the results was identified.

摘要

在新生大鼠单个分离的心室肌细胞中检测了河豚毒素(TTX)敏感的钠电流。使用膜片钳方法测量单通道电流和全细胞电流。通道密度计算为2/μm²,这与我们通常在每个膜片上发现四个通道的结果一致。在20℃时,单通道电导为20 pS。在膜电位从-60到-40 mV时,开放时间分布符合单指数函数,平均开放时间约为1.0 ms。当进行缩放时,平均单通道电流和全细胞电流相似,并且显示出快速和缓慢的失活速率。对于细胞贴附式以及切除式膜片上的通道,失活和激活门控迅速向超极化电位移动,而在全细胞中发生的移动则慢得多。在电位高达-40 mV时,全细胞和单通道电流测量中均存在缓慢失活电流。在全细胞测量中,电位范围可以扩大,并且在电位高达-10 mV时存在缓慢失活。将稳态激活和失活与膜电位相关的曲线几乎没有重叠,并且缓慢失活发生在重叠电位正向的电位处。通过这种方式,缓慢失活与重叠或窗口电流是可区分的,并且缓慢失活电流可能有助于大鼠心脏动作电位的平台期。在极少数情况下,观察到另一组具有较小单位电导和较短持续时间的钠通道。然而,未发现如Gilly和Armstrong(1984年。《自然》[伦敦]。309:448)所描述的单独一组阈值通道。对于常见的钠通道,一些样本中的开放次数远远超过每个膜片上的通道数量,并且首次开放的延迟或等待时间没有充分分散以解释缓慢失活电流:缓慢失活是由通道重新开放产生的。开发了一个通用模型来预测每个样本中的开放次数。每个样本中的开放次数归因于等待时间分散并结合从开放到吸收性失活状态的快速转变的模型并不令人满意,并且确定了一个与结果更一致的模型。