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.


CONCLUSIONS
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.
Hong
Y
Y
Department of Physiology, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Puil
E
E
Mathers
D A
DA
D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002536:Cerebral Arteries / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004594:Electrophysiology; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D015221:Potassium Channels; D002118:Calcium; D006221:Halothane