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

Abstract

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, [MgATP^¨-]=2, [creatine phosphate^¨-]=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°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 atpCa=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.