Pharmacological Roles of the Large-Conductance Calcium-Activated Potassium Channel

Abstract

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.

The Inhibition by Oxaliplatin, a Platinum-Based Anti-Neoplastic Agent, of the Activity of Intermediate-Conductance Ca2+-Activated K+ Channels in Human Glioma Cells

“…To detect the activity of BK Ca channels, cells were bathed in high-K + solution which contained 1.8 mM CaCl 2 . Consistent with previous observations [7,33], as the cells were held at +60 mV, BK Ca -channel activity can be readily detected (Fig. 8).…”

The inhibition by di(2-ethylhexyl)-phthalate of erg-mediated K+ current in pituitary tumor (GH3) cells

“…BK Cachannel activity was noted to be active at the level of resting potential (Wu et al 2006). Therefore, it is anticipated that the inhibition of BK Ca channels and I K(erg) in pituitary lactotrophs caused by DEHP or other phthalate esters may synergistically act to affect the functional activity of these cells in vivo (Wu et al 2000).…”

“…However, no significant change in the single-channel conductance was seen in the presence of DEHP. Alternatively, verruculogen (1 lM), known to block BK Ca channels (Wu et al 2006), was effective in decreasing channel activity in these cells (Fig. 7b).…”

Potent Activation of Large-Conductance Ca2+-Activated K+ Channels by the Diphenylurea 1,3-Bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in Pituitary Tumor (GH3) Cells

“…The channel is unique in that it can be dually activated by membrane depolarization and elevations in intracellular Ca 2ϩ concentrations. Organic compounds with varying structures capable of activating BK Ca channels have been reported previously (Calderone, 2002;Wu et al, 2006;Nardi and Olesen, 2008). Because of their unique high conductance (ϳ200 pS), even at low probability of opening, sufficient current could flow, thereby altering the membrane potential of excitable cells.…”