Neuronal sodium channels in ventricular heart cells are localized near T-tubules openings

Neuronal sodium channels in ventricular heart cells are localized near T-tubules openings
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DOI:
10.1016/j.bbrc.2005.06.203
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发表时间:
2005-09-09
影响因子:
3.1
通讯作者:
Duclohier, H
Duclohier, H
中科院分区:
生物学4区
文献类型:
--
作者:
Duclohier, H

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已知心脏电压依赖性钠通道(VDSC)具有河豚毒素(TTX)抗性。然而,最近的免疫化学研究表明,心脏中存在TTX敏感的神经元型VDSC。扫描离子电导显微镜(SICM)与电生理学结合用于获得更直接的功能证据。比较对照组和去微管组细胞全细胞钠电流(I-Na)的TTX敏感性。加入200 nM TTX可降低I-Na。对照组细胞减少20%,而去微管细胞几乎不受影响。剩余的电流稍早达到峰值,失活衰减更快(如在神经元VDSC)比去微管细胞。单通道活性首先在质膜上随机测定,并且在通过SICM揭示地形后,在修补的T-小管开口处测定。在后一种情况下,观察到11-12 pS的单通道电导,成功率较高。这项研究为心肌细胞中神经元VDSC提供了独立的证据,在那里它们可以快速和同步地偶联T-小管和细胞表面去极化。(c)2005年爱思唯尔公司All rights reserved.
Cardiac voltage-dependent sodium channels (VDSC) are known to be tetrodotoxin (TTX)-resistant. However, recent immunochemical studies suggest the presence of TTX-sensitive neuronal-type VDSC in the heart. Scanning ion conductance microscopy (SICM) coupled to electrophysiology was used to obtain more direct functional evidence. TTX sensitivities of whole-cell sodium currents (I-Na) in control and detubulated cells were compared. Addition of 200 nM TTX decreased I-Na. of control cells by 20%, whereas detubulated cells were hardly effected. The remaining current peaked slightly earlier and inactivation decay was faster (as in neuronal VDSC) than in detubulated cells. Single-channel activity was first assayed at random on the plasmalemma, and after topography had been revealed by SICM, at patched T-tubules openings. In the latter case, a single-channel conductance of 11-12 pS was observed with a higher rate of success. This study provides independent evidence for neuronal VDSC in cardiomyocytes where they could rapidly and synchronously couple T-tubule and cell surface depolarizations. (c) 2005 Elsevier Inc. All rights reserved.