Effects of halothane on Ca2+-activated tension development in mechanically disrupted rabbit myocardial fibers

The effect of halothane on maximal and submaximal Ca2+-activated tension in mechanically disrupted right ventricular papillary muscle from rabbits was studied. Steady-state isometric tension generation was measured in the muscle bundle. The relaxing solution contained (in mM) [Mg2+] = 1, [K+] = 70, [MgATP2-] = 2, [creatine phosphate2-] = 15, [EGTA total] = 7 and imidazole proprionate. The contracting solution contained in addition Ca2+ in various concentrations. In all solutions ionic strength was maintained at 0.15 and pH at 7.00 +/- 0.02 at 20 degrees C. Each fiber bundle was immersed in control solutions equilibrated with 100% N2 and test solutions equilibrated with various concentrations of halothane-N2 mixture. Increasing doses of halothane (1--4%) significantly shifted the relationship between Ca2+ and tension towards higher [Ca2+] and depressed the maximum Ca2+-activated tension. The maximum tension generated at pCa = 3.8 was depressed 5% per 1% increase in halothane concentration. The percentage of maximum tension at submaximum Ca2+ concentrations (pCa = 5.6--5.0) was not significantly decreased until halothane concentration was greater than 2%. It is concluded that halothane slightly but significantly depressed the interactions of contractile proteins and to a lesser degree Ca2+-activation of the regulatory proteins. The halothane-induced depression was completely reversible.