Effect of halothane on large-conductance calcium-dependent potassium channels in cerebrovascular smooth muscle cells of the rat

Abstract

Background: Patch-clamp methods were used to examine the effects of the volatile general anesthetic halothane on large-conductance calcium-dependent potassium channels (BK channels) in dispersed cerebrovascular smooth muscle cells of adult rats. Methods: Inside-out membrane patches were used for recordings at 21-23°C. Halothane was administered at aqueous concentrations of 0.5-2.8 mM in conjunction with free cytoplasmic calcium concentrations of 1 or 100 μM and at a membrane potential of -60 mV or +60 mV. Results: At a free cytoplasmic calcium concentration of 1 μM, the clinically relevant dose of 0.5 mM (2 MAC) halothane reduced the open probability of large-conductance calcium-dependent potassium channels without altering the single-channel conductance. This effect was blocked by increasing the concentration of cytoplasmic free calcium to 100 μM, but was not intrinsically voltage dependent. Conclusion: The marked dilation of cerebral vessels seen during surgical anesthesia with halothane cannot be attributed to direct effects of the drug on large-conductance calcium-dependent potassium channels. The protective effect of calcium suggests that halothane exerts its effects at channel sites located within the cell membrane.