Intracellular renin alters the electrical properties of the intact heart ventricle of adult Sprague Dawley rats

Abstract

The influence of intracellular renin injection on the electrical properties of the intact left ventricle from adult Sprague Dawley rat heart was investigated. Intracellular renin injection was performed using intracellular microelectrodes filled with solution containing renin (120pM). Pressure pulses (40-70psi) for short periods of time (20ms), were applied to the micropipette while recording the action potential simultaneously from the same fiber. The results indicated that intracellular renin caused a depolarization of ventricular fibers of 7.3±2±mV (n=38) (4 animals) (P<0.05) and a decrease of the action potential duration at 50% and at 90% repolarization, respectively. Moreover, the refractoriness was significantly decreased with consequent generation of triggered activity. The effect of intracellular renin was seen within 3min of enzyme injection. The shortening of the action potential was related to an increase of potassium current which was measured in isolated ventricular myocytes before and after intracellular dialysis of renin (10(-9)M) using a voltage whole cell clamp configuration. Valsartan (10(-8)M) dialyzed together with renin (120pM) into the cell decreased drastically the effect of renin on potassium current. An increment of potassium current was also found when intracellular renin was dialyzed into cardiomyocytes exposed to Krebs solution containing valsartan (10(-8)M) for 10min prior to renin administration. Bis-1 which is a specific inhibitor of PKC, abolished the effect of intracellular renin on potassium current.

In conclusion: intracellular renin decreases the action potential duration and cardiac refractoriness in the intact left ventricle of adult Sprague Dawley rats. The shortening of the action potential was related to an increase in total potassium current. The effect of renin on total potassium currents was inhibited by valsartan and by Bis-1. Implication for cardiac arrhythmias was discussed.