Structure and Functional Characterization of a Novel Human Low‐Voltage Activated Calcium Channel

We have isolated and characterized overlapping cDNAs encoding a novel, voltage-gated Ca 2+ channel α 1 subunit, α 1H , from a human medullary thyroid carcinoma cell line. The α 1H subunit is structurally similar to previously described α 1 subunits. Northern blot analysis indicates that α 1H mRNA is expressed throughout the brain, primarily in the amygdala, caudate nucleus, and putamen, as well as in several nonneuronal tissues, with relatively high levels in the liver, kidney, and heart. Ba 2+ currents recorded from human embryonic kidney 293 cells transiently expressing α 1H activated at relatively hyperpolarized potentials (-50 mV), rapidly inactivated (τ = 17 ms), and slowly deactivated. Similar results were observed in Xenopus oocytes expressing α 1H . Single-channel measurements in human embryonic kidney 293 cells revealed a single-channel conductance of ∼9 pS. These channels are blocked by Ni 2+ (IC 50 = 6.6 μM) and the T-type channel antagonists mibefradil (∼50% block at 1 μM) and amiloride (IC 50 = 167 μM). Thus, α 1H -containing channels exhibit biophysical and pharmacological properties characteristic of low voltage-activated, or T-type, Ca 2+ channels.