Effects of chloride replacement in cardiac muscle: Mechanisms of positive inotropy

Abstract

Replacement of chloride ions by various substitutes prolongs the cardiac action potential and has a positive inotropic effect (PIE) in frog myocardium. The underlying mechanisms of 99% chloride substitution by several anions (methanesulfonate, l-pyroglutamate, propionate, methylsulfate and nitrate) were analyzed in frog atrial muscle using a voltage-clamp technique. With all five chloride substitutes the amplitude of slow inward current was increased. This increase was TTX-insensitive (3 × 10 −6 g/ml) and was present in Ca-free media but not in Na-free solutions. The PIE of chloride substitution was due to an increase in both components of contraction (phasic and tonic), and was absent in Na-free solutions. Furthermore, the positive inotropy was more pronounced at lower frequencies of stimulation and in the presence of bicarbonate than it was when Hepes was used. Various mechanisms that may be involved in PIE of chloride-substituted media are discussed.