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 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 approximately 500 ms, followed by a decline over 1-2 min to a steady-state level. The magnitudes of both the peak Na+ pump current (Ip) 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 Ip 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.
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Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Zou
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A
Nonaka
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Zubair
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I
Sanguinetti
M C
MC
Barry
W H
WH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D004789:Enzyme Activation / Q000502:physiology; D017136:Ion Transport / Q000502:physiology; D051379:Mice; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D016276:Ventricular Function
D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium