Structure and functional characterization of a novel human low-voltage activated calcium channel

We have isolated and characterized overlapping cDNAs encoding a novel, volt age-gated Ca2+ channel alpha(1) subunit, alpha(1H), from a human medullary thyroid carcinoma cell fine. The alpha(1H) subunit is structurally similar to previously described alpha(1) subunits. Northern blot analysis indicates that alpha(1H) mRNA is expressed throughout the brain, primarily in the am ygdala, caudate nucleus, and putamen, as well as in several nonneuronal tis sues, with relatively high levels in the liver, kidney, and heart. Ba2+ cur rents recorded from human embryonic kidney 293 cells transiently expressing alpha(1H) activated at relatively hyperpolarized potentials (-50 mV), rapi dly inactivated (tau = 17 ms), and slowly deactivated. Similar results were observed in Xenopus oocytes expressing alpha(1H). Single-channel measureme nts in human embryonic kidney 293 cells revealed a single-channel conductan ce of similar to 9 pS. These channels are blocked by Ni2+ (IC50 = 6.6 mu M) and the T-type channel antagonists mibefradil (similar to 50% block at 1 m u M) and amiloride (IC50 = 167 mu M). Thus, alpha(1H)-containing channels e xhibit biophysical and pharmacological properties characteristic of low vol tage-activated, or T-type, Ca2+ channels.