Sugiura H, Joyner R W
Todd Franklin Cardiac Research Laboratory, Department of Pediatrics, Emory University, Atlanta, Georgia 30323.
Am J Physiol. 1992 Nov;263(5 Pt 2):H1591-604. doi: 10.1152/ajpheart.1992.263.5.H1591.
We used cell pairs electrically coupled with relatively high intercellular resistance to investigate the involvement of calcium current in the origin of the source current during the conduction process of the action potential (AP). Three interventions were used to reduce the calcium current: a specific calcium channel blocker [nifedipine (NIF)], premature stimulation, and increments in the frequency of stimulation of the cell. The ionic membrane current (Iion) after the peak of the AP of the stimulated cell was positive and small when the cell was uncoupled. However, when the stimulated cell was coupled to a cell model or to another cell, Iion during this period became negative and large to supply the coupling current. A rapid early repolarization of the AP occurred in the stimulated cell because of the removal of charge from the stimulated cell. NIF decreased the magnitude of the net negative Iion during this period and caused a more rapid early repolarization in the stimulated cell. NIF increased the delay between the activations of two coupled cells at a given coupling resistance (Rc) but decreased the longest delay that could be produced without conduction failure for a given cell pair. The highest Rc below which conduction of AP occurred was also decreased by NIF. Premature stimulation and an increase of the stimulation frequency also caused an increase in the extent of the early repolarization and increased the delay between two cell activations at a given Rc. Conduction block occurred with sufficient prematurity or at a sufficiently high frequency of stimulation even though activation of the stimulated cell occurred for each stimulus. The Iion that flows during the early plateau phase of the AP in the stimulated cell became negative and significantly large by coupling two cardiac cells together. This current flow is a major component needed to supply the coupling current through the intercellular resistance. The decrease of calcium current caused a decrease in the magnitude of this net inward ionic current, resulting in an increase of the rate of early repolarization and an increase in the conduction delay between two cells at a given Rc. These results suggest the involvement of calcium current in the conduction process when cells are coupled at relatively high Rc.
我们使用细胞间电阻相对较高的电耦合细胞对,来研究钙电流在动作电位(AP)传导过程中源电流产生机制中的作用。采用了三种干预措施来降低钙电流:一种特异性钙通道阻滞剂[硝苯地平(NIF)]、过早刺激以及增加细胞刺激频率。当细胞未耦合时,受刺激细胞动作电位峰值后的离子膜电流(Iion)为正且较小。然而,当受刺激细胞与细胞模型或另一个细胞耦合时,在此期间Iion变为负且较大,以提供耦合电流。由于受刺激细胞电荷的移除,其动作电位出现快速早期复极化。NIF在此期间降低了净负向Iion的幅度,并使受刺激细胞的早期复极化更快。在给定耦合电阻(Rc)下,NIF增加了两个耦合细胞激活之间的延迟,但对于给定细胞对,降低了无传导失败情况下可能产生的最长延迟。NIF还降低了AP发生传导的最低Rc。过早刺激和刺激频率增加也会导致早期复极化程度增加,并在给定Rc下增加两个细胞激活之间的延迟。即使每次刺激都能使受刺激细胞激活,但在足够早的刺激或足够高的刺激频率下仍会发生传导阻滞。通过将两个心肌细胞耦合在一起,受刺激细胞动作电位早期平台期期间流动的Iion变为负且显著增大。这种电流流动是通过细胞间电阻提供耦合电流所需的主要成分。钙电流的减少导致这种内向净离子电流幅度减小,从而导致早期复极化速率增加以及在给定Rc下两个细胞之间的传导延迟增加。这些结果表明,当细胞在相对较高的Rc下耦合时,钙电流参与了传导过程。