Potassium current and sodium pump involvement in the positive inotropy of cardiac muscle during hyperosmotic stress

OBJECTIVE: To identify factors involved in the modification of cardiac electromechanical activity caused by hyperosmotic solution. DESIGN: Membrane potentials and contractions were recorded from isolated papillary muscles, and membrane ionic currents were measured in isolated ventricular myocytes by using the ruptured patch or perforated patch voltage clamp method. ANIMALS AND METHODS: Adult male guinea-pigs weighing 250 to 350 g were used. Normal Tyrode's solution for superfusing experimental preparations was replaced with hyperosmotic Tyrode's solution for observation periods of up to 10 mins. The hyperosmotic solution was normal Tyrode's solution supplemented with 50 or 150 mM sucrose (1.2 or 1.5 times normal osmolality). Sodium pump activity (hyperpolarization in muscles; outward current in myocytes) was activated by switching to pump-activating cation (cesium, potassium) solution from pump-inactivating potassium-free solution under conditions in which other ionic currents were suppressed. RESULTS: Hyperosmotic solution lengthened action potentials and enhanced developed tension in papillary muscles, Superfusion of myocytes with hyperosmotic solution inhibited inward L-type calcium current (I(Ca.L)) by approximately 30% and the outward delayed rectifier potassium current (I(K)) by approximately 50%. Hyperosmotic treatment also partially inhibited sodium pump-generated hyperpolarizations in papillary muscles. However, sodium pump current in myocytes was relatively small under isosmotic conditions and, therefore, unlikely to be a major factor in action potential lengthening. CONCLUSIONS: Inhibition of potassium current is a major factor in the lengthening of the action potential by hyperosmotic solution. It seems likely that the accompanying positive inotropy is due to an elevation of intracellular calcium caused by enhanced calcium influx related to action potential prolongation and sodium pump inhibition.