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

The gating of large-conductance Ca²⁺-activated K⁺ (BK_ca) 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 BK_ca 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 BK^ca channels recorded from pituitary GH₃ 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, cinnamy1-3,4-dihydroxy-α-cyanocinnamate, could directly increase the activity of BK_ca channels in GH₃ cells. CAPE also reduced the frequency and amplitude of intracellular Ca₂₊ oscillations in these cells. The CAPE-stimulated activity in BK_ca channels is thought to be unassociated with its inhibition of NF-κB activation. Cilostazol, an inhibitor of cyclic nucleotide phosphodiesterase, could stimulate BK_ca channel-activity and reduce the firing of action currents simultaneously in GH₃ cells. Therefore, the regulation by these compounds of BK_ca channels may in part be responsible for their regulatory actions on cell functions.