Inactivation influences the extent of inhibition of voltage-gated Ca⁺² channels by Gem-implications for channelopathies.

ABSTRACT: Voltage-gated Ca²⁺ channels (VGCC) directly control muscle contraction and neurotransmitter release, and slower processes such as cell differentiation, migration, and death. They are potently inhibited by RGK GTP-ases (Rem, Rem2, Rad, and Gem/Kir), which decrease Ca²⁺ channel membrane expression, as well as directly inhibit membrane-resident channels. The mechanisms of membrane-resident channel inhibition are difficult to study because RGK-overexpression causes complete or near complete channel inhibition. Using titrated levels of Gem expression in Xenopus oocytes to inhibit WT P/Q-type calcium channels by ∼50%, we show that inhibition is dependent on channel inactivation. Interestingly, fast-inactivating channels, including Familial Hemiplegic Migraine mutants

SUBMITTER: Allam S 

PROVIDER: S-EPMC10466392 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature