Specific Properties of T-type Calcium Channels Generated by the Human alpha sub(1I) Subunit

We have cloned and expressed a human alpha sub(1I) subunit that encodes a subtype of T-type calcium channels. The predicted protein is 95% homologous to its rat counterpart but has a distinct COOH-terminal region. Its mRNA is detected almost exclusively in the human brain, as well as in adrenal and thyroid glands. Calcium currents generated by the functional expression of human alpha sub(1I) and alpha sub(1G) subunits in HEK-293 cells were compared. The alpha sub(1I) current activated and inactivated similar to 10 mV more positively. Activation and inactivation kinetics were up to six times slower, while deactivation kinetics was faster and showed little voltage dependence. A slower recovery from inactivation, a lower sensitivity to Ni super(2+) ions (IC sub(50) similar to 180 mu M), and a larger channel conductance ( similar to 11 picosiemens) were the other discriminative features of the alpha sub(1I) current. These data demonstrate that the alpha sub(1I) subunit encodes T-type Ca super(2+) channels functionally distinct from those generated by the human alpha sub(1G) or alpha sub(1H) subunits and point out that human and rat alpha sub(1I) subunits have species-specific properties not only in their primary sequence, but also in their expression profile and electrophysiological behavior.