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: M embrane potentials and contractions were recorded from isolated papill ary muscles, and membrane ionic currents were measured in isolated ven tricular myocytes by using the ruptured patch or perforated patch volt age clamp method. ANIMALS AND METHODS: Adult-male guinea pigs weighing 250 to 350 g were used. Normal Tyrode's solution for superfusing expe rimental preparations was replaced with hyperosmotic Tyrode's solution for observation periods of up to 10 mins. The hyperosmotic solution w as normal Tyrode's solution supplemented with 50 or 150 mM sucrose (1. 2 or 1.5 times normal osmolality). Sodium pump activity (hyperpolariza tion in muscles; outward current in myocytes) was activated by switchi ng to pump-activating cation (cesium, potassium) solution from pump-in activating potassium-free solution under conditions in which other ion ic 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,I-L) by approximately 30% and the outward delayed rectifier potassium current (I-K) by approximately 50%. Hyper osmotic treatment also partially inhibited sodium pump-generated hyper polarizations in papillary muscles. However, sodium pump current in my ocytes was relatively small under isosmotic conditions and, therefore, unlikely to be a major factor in action potential lengthening. CONCLU SIONS: Inhibition of potassium current is a major factor in the length ening of the action potential by hyperosmotic solution. It seems likel y that the accompanying positive inotropy is due to an elevation of in tracellular calcium caused by enhanced calcium influx related to actio n potential prolongation and sodium pump inhibition.