Attenuation by phentolamine of hypoxia and levcromakalim-induced abbreviation of the cardiac action potential.

1. The effects of phentolamine (5-30 microM) and glibenclamide (10 microM) on action potential characteristics were examined in guinea-pig papillary muscle exposed to either hypoxia or levcromakalim (20 microM). 2. The hypoxia-induced abbreviation of action potential duration (APD) and effective refractory period (ERP) were attenuated but not abolished by glibenclamide (10 microM). Hypoxia reduced APD by 24 +/- 2 vs 65 +/- 4% in glibenclamide- and vehicle-treated tissue, respectively. 3. Phentolamine (10-30 microM) was less effective than glibenclamide in attenuating the hypoxic shortening of APD since APD was reduced by 38 +/- 10, 51 +/- 6% vs 65 +/- 4% in 10 and 30 microM phentolamine and vehicle-treated muscle, respectively. 4. Phentolamine, at concentrations of 10 and 30 microM, also reduced the upstroke velocity of the action potential and at 5 microM it increased the APD from 193 +/- 9 to 221 +/- 12 ms. 5. Glibenclamide completely abolished and phentolamine (30 microM) significantly attenuated levcromakalim-induced changes in duration and ERP. Levcromakalim reduced APD by 71 +/- 2 and 55 +/- 2% in control and phentolamine pretreated muscle, respectively. 6. It is concluded that phentolamine may block KATP channels at concentrations that also block sodium channels.