INFLUENCE OF PRIOR NA+ PUMP ACTIVITY ON PUMP AND NA+ CA2+ EXCHANGE CURRENTS IN MOUSE VENTRICULAR MYOCYTES/

We examined the dependence of peak Na+ pump and Na+/Ca2+ exchanger cur rents on prior Na+ pump inhibition induced by exposure to zero extrace llular K+ in voltage-clamped adult murine ventricular myocytes. Abrupt activation of the Na+ pump by reexposure of myocytes to extracellular K+ with a rapid solution switcher resulted in the development of a tr ansient peak current at similar to 500 ms, followed by a decline over 1-2 min to a steady-state level. The magnitudes of both the peak Na+ p ump current (I-p) and the peak outward Na+/Ca2+ exchange current, acti vated by rapidly reducing extracellular Na+ to zero with the solution switcher, were dependent on previous Na+ pump activity. [Na+] gradient s (Na+-binding benzofuran isophthalate fluorescence) between the patch pipette and the bulk cytosol were relatively small and could not acco unt for the large differences between peak and steady-state I-p and re verse Na+/Ca2+ exchanger currents. Our results are consistent with the presence of a subsarcolemmal Na+ concentration gradient, which is sim ilar for the Na+ pump and the Na+/Ca2+ exchanger. These findings also support the hypothesis that the Na+ pump and the Na+/Ca2+ exchanger ar e colocalized in the sarcolemma.