Halothane and Isoflurane Decrease the Open State Probability of Potassium sup + Channels in Dog Cerebral Arterial Muscle Cells

Background: Both halothane and isoflurane evoke cerebral vasodilation. One of the potential mechanisms for arterial vasodilation is enhanced Potassium sup + efflux resulting from an increased opening frequency of membrane Potassium sup + channels. The current study was designed to determine the effects of volatile anesthetics on Potassium sup + channel current in single vascular smooth muscle cells isolated from dog cerebral arteries.

Methods: Patch clamp recording techniques were used to investigate the effects of volatile anesthetics on macroscopic and microscopic Potassium sup + channel currents.

Results: In the whole-cell patch-clamp mode, in cells dialyzed with pipette solution containing 2.5 mM EGTA and 1.8 mM CaCl2, depolarizing pulses from 60 to +60 mV elicited an outward Potassium sup + current that was blocked 65 plus/minus 5% by 3 mM tetraethylammonium (TEA). Halothane (0.4 and 0.9 mM) depressed the amplitude of this current by 18 plus/minus 4% and 34 plus/minus 6%, respectively. When 10 mM EGTA was used in the pipette solution to strongly buffer intracellular free Calcium2+, an outward Potassium sup + current insensitive to 3 mM TEA was elicited. This Potassium sup + current, which was reduced 51 plus/minus 4% by 1 mM 4-aminopyridine, was also depressed by 17 plus/minus 5 and 29 plus/minus 7% with application of 0.4 and 0.9 mM halothane, respectively. In cell-attached patches using 145 mM KCl in the pipette solution and 5.2 mM KCl in the bath, the unitary conductance of the predominant channel type detected was 99 pS. External application of TEA (0.1 to 3 mM) reduced the unitary current amplitude of the 99 pS Potassium sup + channel in a concentration-dependent manner. The open state probability of this 99 pS Potassium sup + channel was increased by 1 micro Meter Calcium2+ ionophore (A23187). These findings indicate that the 99 pS channel measured in cell-attached patches was a TEA-sensitive, Calcium2+ -activated Potassium sup + channel. Halothane and isoflurane reversibly decreased the open state probability (NPo), mean open time, and frequency of opening of this 99 pS Potassium sup + channel without affecting single channel amplitude or the slope of the current-voltage relationship.