Structure, gating, and pharmacology of human Ca_V3.3 channel.

ABSTRACT: The low-voltage activated T-type calcium channels regulate cellular excitability and oscillatory behavior of resting membrane potential which trigger many physiological events and have been implicated with many diseases. Here, we determine structures of the human T-type Ca_V3.3 channel, in the absence and presence of antihypertensive drug mibefradil, antispasmodic drug otilonium bromide and antipsychotic drug pimozide. Ca_V3.3 contains a long bended S6 helix from domain III, with a positive charged region protruding into the cytosol, which is critical for T-type Ca_V channel activation at low voltage. The drug-bound structures clearly illustrate how these structurally different compounds bind to the same central cavity inside the Ca_V3.3 channel, but

SUBMITTER: He L 

PROVIDER: S-EPMC9019099 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature