Pharmacological roles of the large-conductance calcium-activated potassium channel

The gating of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel is primarily controlled by intracellular Ca(2+) 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 BK(Ca) channel to increase the amplitude of Ca(2+)-activated K(+) current in coronary smooth muscle cells. Its stimulatory effect is related to intracellular Ca(2+) concentrations. In inside-out patches, application of ceramide to the bath suppressed the activity of BK(Ca) channels recorded from pituitary GH(3) cells and from retinal pigment epithelial cells. ICI-182,780, an estrogen receptor antagonist, was found to modulate BK(Ca)-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, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate, could directly increase the activity of BK(Ca) channels in GH(3) cells. CAPE also reduced the frequency and amplitude of intracellular Ca(2+) oscillations in these cells. The CAPE-stimulated activity in BK(Ca) channels is thought to be unassociated with its inhibition of NF-kappaB activation. Cilostazol, an inhibitor of cyclic nucleotide phosphodiesterase, could stimulate BK(Ca) channel-activity and reduce the firing of action currents simultaneously in GH(3) cells. Therefore, the regulation by these compounds of BK(Ca) channels may in part be responsible for their regulatory actions on cell functions.