Influence of prior Na+ pump activity on pump and Na+/Ca2+exchange currents in mouse ventricular myocytes

Abstract

We examined the dependence of peak Na+ pump and Na+/Ca2+exchanger currents on prior Na+pump inhibition induced by exposure to zero extracellular 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 transient peak current at ∼500 ms, followed by a decline over 1–2 min to a steady-state level. The magnitudes of both the peak Na+ pump current ( I p) and the peak outward Na+/Ca2+exchange current, activated by rapidly reducing extracellular Na+ to zero with the solution switcher, were dependent on previous Na+ pump activity. [Na+] gradients (Na+-binding benzofuran isophthalate fluorescence) between the patch pipette and the bulk cytosol were relatively small and could not account for the large differences between peak and steady-state I p and reverse Na+/Ca2+exchanger currents. Our results are consistent with the presence of a subsarcolemmal Na+ concentration gradient, which is similar for the Na+ pump and the Na+/Ca2+exchanger. These findings also support the hypothesis that the Na+ pump and the Na+/Ca2+exchanger are colocalized in the sarcolemma.