Harvey R D, Ten Eick R E
Department of Pharmacology, Northwestern University, Chicago, Illinois 60611.
J Gen Physiol. 1988 Apr;91(4):593-615. doi: 10.1085/jgp.91.4.593.
Whole-cell membrane currents were measured in isolated cat ventricular myocytes using a suction-electrode voltage-clamp technique. An inward-rectifying current was identified that exhibited a time-dependent activation. The peak current appeared to have a linear voltage dependence at membrane potentials negative to the reversal potential. Inward current was sensitive to K channel blockers. In addition, varying the extracellular K+ concentration caused changes in the reversal potential and slope conductance expected for a K+ current. The voltage dependence of the chord conductance exhibited a sigmoidal relationship, increasing at more negative membrane potentials. Increasing the extracellular K+ concentration increased the maximal level of conductance and caused a shift in the relationship that was directly proportional to the change in reversal potential. Activation of the current followed a monoexponential time course, and the time constant of activation exhibited a monoexponential dependence on membrane potential. Increasing the extracellular K+ concentration caused a shift of this relationship that was directly proportional to the change in reversal potential. Inactivation of inward current became evident at more negative potentials, resulting in a negative slope region of the steady state current-voltage relationship between -140 and -180 mV. Steady state inactivation exhibited a sigmoidal voltage dependence, and recovery from inactivation followed a monoexponential time course. Removing extracellular Na+ caused a decrease in the slope of the steady state current-voltage relationship at potentials negative to -140 mV, as well as a decrease of the conductance of inward current. It was concluded that this current was IK1, the inward-rectifying K+ current found in multicellular cardiac preparations. The K+ and voltage sensitivity of IK1 activation resembled that found for the inward-rectifying K+ currents in frog skeletal muscle and various egg cell preparations. Inactivation of IK1 in isolated ventricular myocytes was viewed as being the result of two processes: the first involves a voltage-dependent change in conductance; the second involves depletion of K+ from extracellular spaces. The voltage-dependent component of inactivation was associated with the presence of extracellular Na+.
采用吸液电极电压钳技术在分离的猫心室肌细胞中测量全细胞膜电流。鉴定出一种内向整流电流,其表现出时间依赖性激活。在膜电位负于反转电位时,峰值电流似乎具有线性电压依赖性。内向电流对钾通道阻滞剂敏感。此外,改变细胞外钾离子浓度会导致反转电位和预期钾电流的斜率电导发生变化。弦电导的电压依赖性呈现出S形关系,在更负的膜电位下增加。增加细胞外钾离子浓度会增加电导的最大水平,并导致该关系发生与反转电位变化成正比的偏移。电流的激活遵循单指数时间进程,激活的时间常数呈现出对膜电位的单指数依赖性。增加细胞外钾离子浓度会导致这种关系发生与反转电位变化成正比的偏移。内向电流的失活在更负的电位下变得明显,导致在 -140 至 -180 mV 之间的稳态电流 - 电压关系出现负斜率区域。稳态失活呈现出S形电压依赖性,失活后的恢复遵循单指数时间进程。去除细胞外钠离子会导致在负于 -140 mV 的电位下稳态电流 - 电压关系的斜率降低,以及内向电流的电导降低。得出的结论是,该电流为IK1,即多细胞心脏标本中发现的内向整流钾电流。IK1激活的钾离子和电压敏感性类似于在青蛙骨骼肌和各种卵细胞标本中发现的内向整流钾电流。分离的心室肌细胞中IK1的失活被认为是两个过程的结果:第一个过程涉及电导的电压依赖性变化;第二个过程涉及细胞外空间中钾离子的耗尽。失活的电压依赖性成分与细胞外钠离子的存在有关。