The effect of pinacidil, an opener of ATP-sensitive K+ (K(ATP)) channels, on large-conductance Ca2+-activated K+ (BK(Ca)) channels was investigated in cultured endothelial cells of human umbilical veins. In whole cell configuration, pinacidil (30 μM) increased the amplitude of K+ outward currents (I(K)). Charybdotoxin (100 nM), but not glibenclamide (10 μM), suppressed pinacidil-induced increase in I(K). Neither carbonyl cyanide m- chlorophenyl hydrazone (CCCP; 10 μM), an inhibitor of mitochondrial Ca2+- uniporter, nor cyclosporin A (200 nM), an inhibitor of the mitochondrial permeability transition pore, affected pinacidil-induced increase in I(K). In inside-out patch configuration, bath application of pinacidil (30 μM) did not change single channel conductance but increased the activity of BK(Ca) channels. Pinacidil (30 μM) shifted the activation curve of BK(Ca) channels to less positive membrane potential by approximately 15 mV. Pinacidil stimulated the activity of these channels in a concentration-dependent manner. The EC50 value for pinacidil-induced channel activity was 20 μM. After BK(Ca) channels had been enhanced by Evans blue (100 μM), subsequent application of pinacidil (100 μM) did not further increase the channel activity. These results clearly indicate that in addition to the activation of K(ATP) channels, pinacidil can also stimulate BK(Ca) channels in endothelial cells. These effects could contribute to the regulation of vascular tone if similar results were found in endothelial cells in vivo.
|頁（從 - 到）||6-16|
|期刊||Drug Development Research|
|出版狀態||Published - 1999 十一月 10|
All Science Journal Classification (ASJC) codes
- Drug Discovery