Properties of Ba super(2+) currents arising from human alpha 1E and alpha 1E beta 3 constructs expressed in HEK293 cells: physiology, pharmacology, and comparison to native T-type Ba super(2+) currents

Currents arising from human alpha 1E and alpha 1E beta 3 Ca super(2+) 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 alpha 1E subunit with the beta 3 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 alpha 1E and alpha 1E beta 3 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 alpha 1E and alpha 1E beta 3 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 alpha 1E and T-type currents, aspects of blockade by amiloride and phenytoin appear to distinguish alpha 1E current from T-type currents. The results define several distinguishing features of alpha 1E currents that distinguish them from native T-type currents.