Sanguinetti M C, Jurkiewicz N K
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Pflugers Arch. 1992 Feb;420(2):180-6. doi: 10.1007/BF00374988.
We sought to determine whether extracellular Ca2+ (Ca2+e) and K+ (K+e) play essential roles in the normal functioning of cardiac K+ channels. Reports by others have shown that removal of Ca2+e and K+e alters the gating properties of neural delayed rectifier (IK) and A-type K+ currents, resulting in a loss of normal cation selectivity and voltage-dependent gating. We found that removal of Ca2+e and K+e from the solution bathing guinea pig ventricular myocytes often induced a leak conductance, but did not affect the ionic selectivity or time-dependent activation and deactivation properties of IK. The effect of [K+]e on the magnitude of the two components of cardiac IK was also examined. IK in guinea pig myocytes is comprised of two distinct types of currents: IKr (rapidly activating, rectifying) and IKs (slowly activating). The differential effect of Ca2+e on the two components of IK (previously shown to shift the voltage dependence of activation of the two currents in opposite directions) was exploited to determine the role of K+e on the magnitude of IKs and IKr. Lowering [K+]e from 4 to 0 mM increased IKs, as expected from the change in driving force for K+, but decreased IKr. The differential effect of [K+]e on the two components of cardiac IK may explain the reported discrepancies regarding modulation of cardiac IK conductance by this cation.
我们试图确定细胞外钙离子（Ca2+e）和钾离子（K+e）在心脏钾通道的正常功能中是否发挥重要作用。其他人的报告表明，去除Ca2+e和K+e会改变神经延迟整流钾电流（IK）和A型钾电流的门控特性，导致正常阳离子选择性和电压依赖性门控丧失。我们发现，从豚鼠心室肌细胞的灌流液中去除Ca2+e和K+e常常会诱发泄漏电导，但不影响IK的离子选择性或时间依赖性激活和失活特性。我们还研究了细胞外钾离子浓度（[K+]e）对心脏IK两个组分大小的影响。豚鼠心肌细胞中的IK由两种不同类型的电流组成：快速激活整流钾电流（IKr）和缓慢激活钾电流（IKs）。利用Ca2+e对IK两个组分的不同影响（先前已证明会使两种电流的激活电压依赖性向相反方向移动）来确定K+e对IKs和IKr大小的作用。正如从钾离子驱动力变化所预期的那样，将[K+]e从4 mM降至0 mM会增加IKs，但会降低IKr。细胞外钾离子浓度（[K+]e）对心脏IK两个组分的不同影响可能解释了关于该阳离子对心脏IK电导调节的报道差异。
