Effect of propofol on hypotonic swelling-induced membrane depolarization in human coronary artery smooth muscle cells.

Abstract

Stretch (mechanical stress)-induced membrane depolarization of smooth muscle may contribute to basal vascular tone and myogenic control. Propofol induces vasodilation and inhibits myogenic control. Hypotonic swelling was used as a model of mechanical stress. The authors investigated the effects of propofol and 5-nitro-2-(3-phenylpropylamino)benzoic acid, a chloride channel and nonselective cation channel blocker, on hypotonicity-induced membrane depolarization in cultured human coronary artery smooth muscle cells. A voltage-sensitive fluorescent dye, bis-(1,3-diethylthiobarbiturate)trimethine oxonol, was used to assess relative changes in membrane potential semiquantitatively. The cells were continuously perfused with Earle's balanced salt solution containing 200 nM bis-(1,3-diethylthiobarbiturate)trimethine oxonol and exposed sequentially to isotonic and hypotonic medium. In a second series of experiments, the cells were exposed to hypotonic media in the presence and absence of 5-nitro-2-(3-phenylpropylamino)benzoic acid or propofol. The relative fluorescence values at 10, 20, and 30% hypotonicity were 147 +/- 29, 214 +/- 74, and 335 +/- 102% of baseline, respectively. The changes were all significantly different from the isotonic time control group. In the presence of 200 microM 5-nitro-2-(3-phenylpropylamino)benzoic acid or 0.1, 1, 10, or 100 microg/ml propofol, the relative fluorescence values at 30% hypotonicity were 87 +/- 17, 194 +/- 27, 160 +/- 18, 130 +/- 18, and 84 +/- 15%, respectively. These changes were significantly less than the 30% for the hypotonic control (246 +/- 23%). These results suggest that volume-sensitive chloride channels and nonselective cation channels may participate in hypotonicity-induced membrane depolarization and that propofol inhibits hypotonicity-induced membrane depolarization in coronary artery smooth muscle.