Differential anesthetic-induced opening of calcium-dependent large conductance channels in isolated ventricular myocytes.
Under conditions of low Ca buffering of the pipette intracellular dialyzing solution, the opening of Ca dependent large conductance (approximately 310 pS) channels (LCCs) was observed in isolated ventricular myocytes using the whole-cell patch clamp technique. With Na-Ca exchange current (INaCa) suppressed by elimination of intracellular and extracellular Na, sustained LCC activity, which is markedly enhanced by caffeine-stimulated Ca release from the sarcoplasmic reticulum (SR), was increased by application of the inhalational anesthetic halothane, but not isoflurane. Halothane (0.90 mM in solution) reversibly increased the frequency of LCC openings, fo, by a factor of approximately 30 with a concurrent rise in the observed probability of opening, NPo, by a factor of approximately 50. The effect of halothane on LCC activation was suppressed by either strong Ca buffering in the whole-cell pipette solution or pretreatment of the myocytes with ryanodine (10 microM) to decrease SR Ca release. In the presence of intracellular and extracellular Na, a transient inward current was evoked by application of caffeine (5 mM) or halothane (1.80 mM) suggesting that Ca release from the SR by either agent can activate INaCa. Our findings are consistent with the notion that halothane, in contrast to isoflurane, causes SR release of Ca. The eventual depletion of SR activator Ca may account, at least in part, for the differential effects of these anesthetics on myocardial tension development.
Pancrazio
J J
JJ
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908.
Lynch
C
C
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007530:Isoflurane / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D000777:Anesthetics; D007473:Ion Channels; D012433:Ryanodine; D002110:Caffeine; D007530:Isoflurane; D002118:Calcium; D006221:Halothane