Alterations in intracellular calcium activity and contractility of isolated perfused rabbit hearts by ionophores and adrenergic agents.

The fluorescent calcium indicator quin2 has been used for the first continuous measurement of the effects of pharmacological agents on intracellular calcium activity in isolated, perfused rabbit hearts. The average intracellular calcium activity was elevated after the infusion of norepinephrine, concurrent with increases in left ventricular pressure and heart rate. These changes were abolished by pretreatment of the heart with phentolamine and nadolol, alpha and beta adrenergic receptor antagonists, respectively. Pretreatment with phentolamine and nadolol did not eliminate the increases in left ventricular pressure and intracellular calcium activity caused by the infusion of the monovalent carboxylic ionophores monensin and salinomycin. It is concluded that the ionophores cause these effects by elevating intracellular sodium activity, which then raises the intracellular calcium activity of the myocardium through intracellular displacement and/or transcellular exchange. It is suggested that the use of fluorescent calcium indicators in intact organs could be useful in evaluating the role of calcium in a variety of pathological states.