Activation of large-conductance Ca2+-activated K+ channels by pinacidil in human umbilical vascular endothelial cells

✍ Scribed by Sheng-Nan Wu; Hui-Fang Li; Ai-Yu Shen

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 329 KB
• Volume: 48
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199909)48:1<6::aid-ddr2>3.0.co;2-b

✦ Synopsis

The effect of pinacidil, an opener of ATP-sensitive K + (K ATP ) channels, on large-conductance Ca 2+ -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 Ca 2+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 EC 50 value for pinacidilinduced 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. Drug Dev. Res. 48:6-16, 1999.