Actions of extracellular chloride ion substitution on contractility of isolated ventricular myocardium

OBJECTIVE: Replacement of extracellular chloride ions by some other anions exerts a positive inotropic effect on isolated cardiac muscle preparations. The aim of this study was to determine whether the increase of force was mediated by an intracellular alkalosis. METHODS: Isometric tension development was measured using guinea pig papillary muscles during replacement of superfusate Cl- with isethionate ions. Intracellular pH and L-type Ca2+ currents were measured in isolated myocytes using epifluorescence microscopy and a switch-clamp technique respectively. RESULTS: Reduction of extracellular Cl- increased tension, a phenomenon which was partially inhibited with the anion exchange blocker SITS. Force was also increased by reducing superfusate PCO2. Reduction of superfusate [Cl-] and PCO2 both produced concentration dependent intracellular alkalosis. The relationship between the changes to tension and intracellular pH was different when either the superfusate [Cl-] or PCO2 was reduced, less pronounced when the [Cl-] was reduced. An increase of the L-type Ca2+ current was produced in low [Cl-] solutions which could be attributed to the accompanying intracellular alkalosis. CONCLUSIONS: The positive inotropic effect of superfusate Cl- removal can only partially be explained by intracellular alkalosis. Other, as yet unknown, changes must determine the remainder of the inotropic response.