DIRECT MEASUREMENT OF L-TYPE CA2+ WINDOW CURRENT IN HEART-CELLS

被引:86
作者
HIRANO, Y [1 ]
MOSCUCCI, A [1 ]
JANUARY, CT [1 ]
机构
[1] UNIV CHICAGO,DEPT MED CARDIOL,CARDIAC ELECTROPHYSIOL LABS,BOX 322,5841 S MARYLAND AVE,CHICAGO,IL 60637
关键词
CA2+ CURRENT; ACTIVATION; INACTIVATION; WINDOW CURRENT; PURKINJE CELLS; HEART;
D O I
10.1161/01.RES.70.3.445
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The activation and inactivation relations of several ion channel currents overlap, suggesting the existence of a steady-state or "window" current. We studied L-type Ca2+ channel window current in single cardiac Purkinje cells using a voltage-clamp protocol by which channels were first inactivated nearly completely during a long-duration depolarizing step, and then the recovery of Ca2+ current was observed during repolarizing steps into the L-type Ca2+ window voltage range. With these conditions, a small-amplitude inward Ca2+ current gradually developed after repolarization to voltages within the window but not after steps to voltages positive or negative to it. Window current was suppressed by Cd2+ (50-mu-M), nifedipine (1-mu-M), and nicardipine (1-mu-M), and it was augmented by isoproterenol (5-mu-M) and Bay K 8644 (1-mu-M). At voltages at which window current developed, L-type Ca2+ channels also recovered to a closed state from which they could be reopened by an additional depolarizing step. At voltages positive to the window range, channel recovery to a closed state(s) was absent, whereas at voltages negative to the window range, channel recovery to a closed state(s) increased, as expected from the "steady-state" inactivation relation. Our results provide direct measurement of L-type Ca2+ window current and distinguish it from other processes, such as slow inactivation. Our findings support the postulate that within a window there occur channel transitions from inactivated to closed states, and these channels (re)open, and this process may occur repetitively. Some physiological and pathophysiological roles for L-type Ca2+ window current are discussed.
引用
收藏
页码:445 / 455
页数:11
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