Ion selectivity of stretch-activated cation currents in mouse ventricular myocytes
Ion selectivity of stretch-activated cation currents in mouse ventricular myocytes
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DOI：
10.1007/s00424-003-1018-y
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发表时间：
2003-05-01
影响因子：
4.5
通讯作者：
Isenberg, G
中科院分区：
文献类型：
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作者：
Kamkin, A;Kiseleva, I;Isenberg, G
牵张激活的非选择性阳离子电流（I-SAC）构成了一种可诱发心律失常的机制。我们研究了I-SAC在小鼠心室肌细胞之间的膜片吸管和电动机驱动的玻璃笔拉伸部分细胞表面。在非钳夹细胞中，局部牵张去极化并诱导后去极化和期外收缩。在电压钳制细胞（K+电流被抑制）中，局部牵张激活的I-SAC在-12和0 mV之间具有接近线性的电压依赖性和反向极性。电导G（SAC）随局部拉伸程度的增加而增加。I-SAC不是Cl-电流（对天冬氨酸替代Cl-不敏感）。I-SAC不是Ca 2+激活电流（对5 mM细胞内BAPTA不敏感）。G（SAC）被5 μ M GdCl 3或75 mM胞外（e.c.）CaCl2.删除e.c. CaCl_2使G（SAC）增加2.5倍，似乎G（SAC）对Ca ~（2+）和Gd ~（3+）敏感。替换150 mM e.c. Na+与150 mM Cs+、Li+、四乙基铵（TEA（+））或N-甲基D-葡糖胺（NMDG（+））产生的电流表明电导的选择性为G（Cs）>G（Na）>G（Li）>G（TEA）>G（NMDG）。I-SAC被细胞松弛素D抑制，好像完整的F-肌动蛋白细胞骨架是激活I-SAC所必需的。
Stretch-activated non-selective cation currents (I-SAC) constitute a mechanism that can induce cardiac arrhythmias. We studied I-SAC in mouse ventricular myocytes by stretching part of the cell surface between the patch-pipette and a motor-driven glass stylus. In non-clamped cells, local stretch depolarised and induced after-depolarisations and extrasystoles. In voltage-clamped cells (K+ currents suppressed) I-SAC activated by local stretch had a nearly linear voltage dependence and reversed polarity between -12 and 0 mV. Conductance G(SAC) increased with the extent of local stretch. I-SAC was not a Cl- current (insensitivity to replacement of Cl- by aspartate). I-SAC was not a Ca2+-activated current (insensitivity to 5 mM intracellular BAPTA). G(SAC) was blocked by 5 muM GdCl3 or by 75 mM extracellular (e.c.) CaCl2. Removal of e.c. CaCl2 increased G(SAC) 2.5-fold, as if G(SAC) were sensitive to Ca2+ and Gd3+. Replacement of 150 mM e.c. Na+ by 150 mM Cs+, Li+, tetraethylammonium (TEA(+)) or N-methyl D-glucosamine (NMDG(+)) yielded currents that suggested for the conductance a selectivity G(Cs)>G(Na)>G(Li)>G(TEA)>G(NMDG). I-SAC was suppressed by cytochalasin D, as if an intact F-actin cytoskeleton were necessary for activation of I-SAC.