Properties of cardiac contractions in zero sodium solutions: Intracellular free calcium controls slow channel conductance

Abstract

Guinea-pig, rat and frog atria bathed in zero sodium, contract in response to high intensity electrical stimuli. A transient positive inotropic response after sodium removal is followed by a decline and then leveling off of twitch tension. Abolition of sodium-calcium exchange in zero sodium medium results in a species-dependent decline in the rate of relaxation and an increase in diastolic tension. The characteristic positive inotropic effect of isoproterenol is reduced in rat and frog atria and abolished in guinea-pig atria bathed in zero sodium. Cyclic AMP generation in response to isoproterenol is reduced but not abolished in zero sodium, and time to peak tension is still shortened in response to the catecholamine. Addition of strontium ion to guinea-pig atria in zero sodium restores the ability of isoproterenol to increase twitch tension and to enhance slow channel conductance now carried by strontium. Chelation of calcium ion in the presence of strontium ion by the calcium chelator ethyleneglycol bis-(β-amino ethylether)- n,n,n′,n′ tetraacetic acid (EGTA) K A Ca K A Sr > 100 greatly increases the duration of slow action potentials carried by strontium. These data suggest that intracellular calcium accumulation, but not strontium accumulation, decreases slow channel conductance and the ability of isoproterenol to enhance slow channel conductance. It is concluded that sodium reduction tends to increase intracellular free calcium by decreasing the process of sodium-calcium exchange which normally contributes to relaxation. A large accumulation of intracellular calcium diminishes the ability of the tissue to respond to isoproterenol both by reducing the ability of the tissue to generate cyclic AMP and by directly inhibiting slow channel conductance.