Nakashima Y M, Todorovic S M, Pereverzev A, Hescheler J, Schneider T, Lingle C J
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Neuropharmacology. 1998 Aug;37(8):957-72. doi: 10.1016/s0028-3908(98)00097-5.
Currents arising from human alpha1E and alpha1Ebeta3 Ca2+ channel subunits expressed in HEK-293 cells were examined with whole-cell recording methods and compared to properties of T-current in DRG neurons studied under identical ionic conditions. Coexpression of alpha1E subunit with the beta3 subunit shifted activation to more negative potentials. Activation and deactivation of both variants were comparable at most voltages, with deactivation becoming faster, but less voltage-dependent, at more negative potentials. The inactivation time course for alpha1E and alpha1Ebeta3 currents was best described by at least two exponential components. Recovery from inactivation was markedly voltage-dependent and similar for both constructs. In comparison to alpha1E and alpha1Ebeta3 constructs, T current activation was shifted to more negative potentials, activation was typically slower, deactivation exhibited a steeper voltage-dependence, and recovery from inactivation was less voltage-dependent. Over most of the activation range, native T current inactivated more completely and in a single exponential fashion. Despite some pharmacological similarities (e.g. octanol, barbiturates) between alpha1E and T-type currents, aspects of blockade by amiloride and phenytoin appear to distinguish alpha1E current from T-type currents. The results define several distinguishing features of alpha1E currents that distinguish them from native T-type currents.
运用全细胞记录方法检测了在HEK - 293细胞中表达的人α1E和α1Eβ3 Ca2+通道亚基产生的电流，并将其与在相同离子条件下研究的背根神经节（DRG）神经元中T型电流的特性进行比较。α1E亚基与β3亚基共表达使激活电位向更负的方向移动。在大多数电压下，两种变体的激活和失活情况相当，在更负的电位下，失活变得更快，但电压依赖性更小。α1E和α1Eβ3电流的失活时间进程最好用至少两个指数成分来描述。从失活状态恢复明显依赖电压，且两种构建体相似。与α1E和α1Eβ3构建体相比，T型电流的激活电位向更负的方向移动，激活通常较慢，失活表现出更陡峭的电压依赖性，从失活状态恢复的电压依赖性较小。在大部分激活范围内，天然T型电流以单一指数方式更完全地失活。尽管α1E电流与T型电流在某些药理学特性上相似（如辛醇、巴比妥类药物），但阿米洛利和苯妥英钠的阻断作用似乎能区分α1E电流与T型电流。这些结果定义了α1E电流与天然T型电流不同的几个显著特征。
