Na+-dependent activation of Na+-K+ pump in human myocardium during recovery from acidosis.
In cardiac cells of some species, an intracellular Na+ load and enhanced electrogenic Na+ pumping can develop during recovery from acidosis. We examined whether this can also occur in human heart. Specimens of human right atrial appendage were incubated in cold (2 degrees C) NH4Cl-substituted (for NaCl) Tyrode solution and then transferred to warm (30 degrees C) Na+-Tyrode solution containing 20 mM K+ to induce an intracellular acid load. After transfer, resting membrane potential (Em) transiently hyperpolarized to a maximal level (Emax) of -58.6 +/- 1.3 mV (n = 8), a level significantly (P less than 0.001) more negative than the equilibrium potential for K+. Decreasing K+ conductance with 0.5 mM Ba2+ increased Emax to -74.0 +/- 2.7 mV (n = 6, P less than 0.001), indicating that the hyperpolarization was not due to efflux of NH+4 through K channels. Acetylstrophanthidin (0.5 microM) reduced Emax to -37.5 +/- 3.1 mV (n = 5, P less than 0.001), indicating that an increased level of Na+-K+ pump activity was involved in the hyperpolarization. The Na+-K+ pump-induced hyperpolarization was abolished (Emax = -22.6 +/- 1.6 mV, n = 8, P less than 0.001) by 10 microM 5-(N,N-dimethyl)amiloride and, when the extracellular Na+ concentration was reduced to 50 mM, by 50 mM Li+. These findings suggest that Na+-H+ exchange can produce a Na+ load which then can stimulate electrogenic Na+ pumping in human cardiac cells during recovery from acidosis.
Rasmussen
H H
HH
Reingold ECG Center, Northwestern University, Chicago, Illinois 60611.
Cragoe
E J
EJ
ten Eick
R E
RE
D000138:Acidosis / Q000201:enzymology*; D000643:Ammonium Chloride / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D008094:Lithium / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology*; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D000643:Ammonium Chloride; D001464:Barium; D008094:Lithium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium