Na/K pump current and [Na](i) in rabbit ventricular myocytes: local [Na](i) depletion and Na buffering.
Na/K pump current (I(pump)) and intracellular Na concentration ([Na](i)) were measured simultaneously in voltage-clamped rabbit ventricular myocytes, under conditions where [Na](i) is controlled mainly by membrane transport. Upon abrupt pump reactivation (after 10-12 min blockade), I(pump) decays in two phases. Initially, I(pump) declines with little [Na](i) change, whereas the second phase is accompanied by [Na](i) decline. Initial I(pump) sag was still present at external [K] = 15 mM, but prevented by [Na](i) approximately 100 mM. Initial I(pump) sag might be explained by subsarcolemmal [Na](i) ([Na](SL)) depletion produced by rapid Na extrusion and I(pump). Brief episodes of pump blockade allowed [Na](SL) repletion, since peak postblockade I(pump) exceeded I(pump) at the end of previous activation (without appreciably altered global [Na](i)). The apparent K(m) for [Na](i) was higher for continuous I(pump) activation than peak I(pump) (14.1 +/- 0.2 vs. 11.2 +/- 0.2 mM), whereas that based on d[Na](i)/dt matched peak I(pump) (11.6 +/- 0.3 mM). [Na](SL) depletion (vs. [Na](i)) could be as high as 3 mM for [Na](i) approximately 18-20 mM. A simple diffusion model indicates that such [Na](SL) depletion requires a Na diffusion coefficient 10(3)- to 10(4)-fold below that expected in bulk cytoplasm (although this could be subsarcolemmal only). I(pump) integrals and [Na](i) decline were used to estimate intracellular Na buffering, which is slight (1.39 +/- 0.09).
Despa
Sanda
S
Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA.
Bers
Donald M
DM
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D003198:Computer Simulation; D004058:Diffusion; D042541:Intracellular Space / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology*; D008954:Models, Biological; D032342:Muscle Cells / Q000502:physiology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D016276:Ventricular Function
D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase