Membrane Potential Hyperpolarization in Mammalian Cardiac Cells by Synchronization Modulation of Na/K Pumps

Abstract

In previously reported work, we developed a new technique, synchronization modulation, to electrically activate Na/K pump molecules. The fundamental mechanism involved in this technique is a dynamic entrainment procedure of the pump molecules, carried out in a stepwise pattern. The entrainment procedure consists of two steps: synchronization and modulation. We theoretically predicted that the pump functions can be activated exponentially as a function of the membrane potential. We have experimentally demonstrated synchronization of the Na/K pump molecules and acceleration of their pumping rates by many fold through use of voltage-clamp techniques, directly monitoring the pump currents. We further applied this technique to intact skeletal muscle fibers from amphibians and found significant effects on the membrane resting potential. Here, we extend our study to intact mammalian cardiomyocytes. We employed a noninvasive confocal microscopic fluorescent imaging technique to monitor electric field–induced changes in ionic concentration gradient and membrane resting potential. Our results further confirm that the well-designed synchronization modulation electric field can effectively accelerate the Na/K pumping rate, increasing the ionic concentration gradient across the cell membrane and hyperpolarizing the membrane resting potential.