Ion-dependent inactivation of barium current through L-type calcium channels

被引:101
作者
Ferreira, G
Yi, JX
Rios, E
Shirokov, R
机构
[1] RUSH UNIV, SCH MED, DEPT PHYSIOL & MOL BIOPHYS, CHICAGO, IL 60612 USA
[2] FAC MED, MONTEVIDEO, URUGUAY
[3] AA BOGOMOLETS PHYSIOL INST, UA-252601 KIEV, UKRAINE
关键词
gating current; signal transduction; cardiac muscle; heterologous expression;
D O I
10.1085/jgp.109.4.449
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
It is widely believed that Bd(2+) currents carried through L-type Ca2+ channels inactivate by a voltage-dependent mechanism similar to that described for other voltage-dependent channels. Studying ionic and gating currents of rabbit cardiac Ca2+ channels expressed in different subunit combinations in tsA201 cells, we found a phase of Ba2+ current decay with characteristics of ion-dependent inactivation. Upon a long duration (20 s) depolarizing pulse, Tga decayed as the sum of two exponentials. The slow phase (tau approximate to 6 s, 21 degrees C) was parallel to a reduction of gating charge mobile at positive voltages, which was determined in the same cells. The fast phase of current decay (7 = 600 ms), involving about 50% of total decay, was not accompanied by decrease of gating currents. Its amplitude depended on voltage with a characteristic U-shape, reflecting reduction of inactivation at positive voltages. When Na+ was used as the charge carrier, decay of ionic current followed a single exponential, of rate similar to that of the slow decay of Ba2+ current. The reduction of Ba2+ current during a depolarizing pulse was not due to changes in the concentration gradients driving ion movement, because Ba2+ entry during the pulse did not change the reversal potential for Ba2+. A simple model of Ca2+-dependent inactivation (Shirokov,R,R. Levis, N. Shirokova, and E. Rios. 1993. J. Gen. Physiol. 102:1005-1030) robustly accounts for fast Ba2+ current decay assuming the affinity of the inactivation site on the alpha(1) subunit to be 100 times lower for Ba2+ than Ca2+
引用
收藏
页码:449 / 461
页数:13
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