The gating of large-conductance Ca2+-activated K+ (BKca) channel is primarily controlled by intracellular Ca2+ and/or membrane depolarization. These channels play a role in the coupling of excitation-contraction and stimulus-secretion. A variety of structurally distinct compounds may influence the activity of these channels. Squamocin, an Annonaceous acetogenin, could interact with the BKca channel to increase the amplitude of Ca2+-activated K+ current in coronary smooth muscle cells. Its stimulatory effect is related to intracellular Ca2+ concentrations. In inside-out patches, application of ceramide to the bath suppressed the activity of BKca channels recorded from pituitary GH3 cells and from retinal pigment epithelial cells. ICI-182,780, an estrogen receptor antagonist, was found to modulate BKca-channel activity in cultured endothelial cells and smooth muscle cells in a mechanism unlinked to the inhibition of estrogen receptors. Caffeic acid phenethyl ester (CAPE) and its analogy, cinnamy1-3,4-dihydroxy-α-cyanocinnamate, could directly increase the activity of BKca channels in GH3 cells. CAPE also reduced the frequency and amplitude of intracellular Ca2+ oscillations in these cells. The CAPE-stimulated activity in BKca channels is thought to be unassociated with its inhibition of NF-κB activation. Cilostazol, an inhibitor of cyclic nucleotide phosphodiesterase, could stimulate BKca channel-activity and reduce the firing of action currents simultaneously in GH3 cells. Therefore, the regulation by these compounds of BKca channels may in part be responsible for their regulatory actions on cell functions.
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