Mechanism and selectivity of the effects of halothane on gap junction channel function

Volatile anesthetics alter tissue excitability by decreasing the extent of gap junction-mediated cell-cell coupling and by altering the activity of th e channels that underlie the action potential. In the present study, we dem onstrate, using dual whole-cell voltage-clamp techniques, that coexpression of connexin (Cx) 40 and Cx43 rendered cells more sensitive to uncoupling b y halothane than cells that express only Cx40 or only Cx43. The halothane-i nduced reduction in junctional conductance was caused by decreased channel mean open time and increased channel mean closed time. The magnitude of the effect of halothane on channel open time was least for Cx40-like channels and greatest for heteromeric channels. Thus, the data indicate that halotha ne gates gap junction channels to the closed state in a dose-dependent and connexin-specific manner. One consequence of the selectivity of halothane i s that the profile of single-channel events observed in the presence of hal othane may not be quantitatively representative of the population of channe ls contributing to macroscopic conductance in cells that express more than one connexin. In addition, in tissues that express multiple connexins, such as heart and blood vessels, the capacity of the gap junctions to transmit electrical and chemical signals in the presence of halothane could vary acc ording to the pattern of connexin expression. The full text of this article is available at http://www.circresaha.org.