DeCoursey T E
Department of Physiology, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois 60612-3864.
J Gen Physiol. 1990 Apr;95(4):617-46. doi: 10.1085/jgp.95.4.617.
Inactivation of K+ channels responsible for delayed rectification in rat type II alveolar epithelial cells was studied in Ringer, 160 mM K-Ringer, and 20 mM Ca-Ringer. Inactivation is slower and less complete when the extracellular K+ concentration is increased from 4.5 to 160 mM. Inactivation is faster and more complete when the extracellular Ca2+ concentration is increased from 2 to 20 mM. Several observations suggest that inactivation is state-dependent. In each of these solutions depolarization to potentials near threshold results in slow and partial inactivation, whereas depolarization to potentials at which the K+ conductance, gK, is fully activated results in maximal inactivation, suggesting that open channels inactivate more readily than closed channels. The time constant of current inactivation during depolarizing pulses is clearly voltage-dependent only at potentials where activation is incomplete, a result consistent with coupling of inactivation to activation. Additional evidence for state-dependent inactivation includes cumulative inactivation and nonmonotonic from inactivation. A model like that proposed by C.M. Armstrong (1969. J. Gen. Physiol. 54: 553-575) for K+ channel block by internal quaternary ammonium ions accounts for most of these properties. The fundamental assumptions are: (a) inactivation is strictly coupled to activation (channels must open before inactivating, and recovery from inactivation requires passage through the open state); (b) the rate of inactivation is voltage-independent. Experimental data support this coupled model over models in which inactivation of closed channels is more rapid than that of open channels (e.g., Aldrich, R.W. 1981. Biophys. J. 36:519-532). No inactivation results from repeated depolarizing pulses that are too brief to open K+ channels. Inactivation is proportional to the total time that channels are open during both a depolarizing pulse and the tail current upon repolarization; repolarizing to more negative potentials at which the tail current decays faster results in less inactivation. Implications of the coupled model are discussed, as well as additional states needed to explain some details of inactivation kinetics.
在任氏液、160 mM K-任氏液和20 mM Ca-任氏液中研究了大鼠II型肺泡上皮细胞中负责延迟整流的钾通道的失活情况。当细胞外钾离子浓度从4.5 mM增加到160 mM时，失活变慢且不完全。当细胞外钙离子浓度从2 mM增加到20 mM时，失活变快且更完全。一些观察结果表明失活是状态依赖性的。在这些溶液中的每一种中，去极化到接近阈值的电位会导致缓慢且部分失活，而去极化到钾离子电导gK完全激活的电位会导致最大失活，这表明开放通道比关闭通道更容易失活。去极化脉冲期间电流失活的时间常数仅在激活不完全的电位下明显依赖于电压，这一结果与失活与激活的耦合一致。状态依赖性失活的其他证据包括累积失活和失活的非单调性。C.M. 阿姆斯特朗（1969年。《普通生理学杂志》54: 553 - 575）提出的关于内部季铵离子对钾通道阻滞的模型解释了这些特性中的大部分。基本假设是：(a) 失活严格与激活耦合（通道必须先开放才能失活，从失活中恢复需要通过开放状态）；(b) 失活速率与电压无关。实验数据支持这种耦合模型，而不支持关闭通道的失活比开放通道更快的模型（例如，奥尔德里奇，R.W. 1981年。《生物物理学杂志》36:519 - 532）。重复的去极化脉冲过于短暂而无法打开钾通道时不会导致失活。失活与去极化脉冲期间以及复极化时尾电流期间通道开放的总时间成正比；复极化到尾电流衰减更快的更负电位会导致失活减少。讨论了耦合模型的含义，以及解释失活动力学一些细节所需的其他状态。
