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

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 degrees C. Halothane was administered at aqueous concentrations of 0.5-2.8 mM in conjunction with free cytoplasmic calcium concentrations of 1 or 100 microM and at a membrane potential of -60 mV or +60 mV.

RESULTS

At a free cytoplasmic calcium concentration of 1 microM, 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 microM, 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.