Subtype-Selective Positive Modulation of K_Ca2.3 Channels Increases Cilia Length.

ABSTRACT: Small-conductance Ca²⁺-activated potassium (K_Ca2.x) channels are gated exclusively by intracellular Ca²⁺. The activation of K_Ca2.3 channels induces hyperpolarization, which augments Ca²⁺ signaling in endothelial cells. Cilia are specialized Ca²⁺ signaling compartments. Here, we identified compound 4 that potentiates human K_Ca2.3 channels selectively. The subtype selectivity of compound 4 for human K_Ca2.3 over rat K_Ca2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of K_Ca2.3 channels by compound 4 increased flow-induced Ca²⁺ signaling and cilia length, while negative modulation by AP14145 reduced flow-induced Ca<

SUBMITTER: Nam YW 

PROVIDER: S-EPMC9396613 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature