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Charge movement during Na+ translocation by native and cloned cardiac Na+/Ca2+ exchanger

Naturevolume 352pages715718 (1991) | Download Citation

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Abstract

Na+/Ca2+ EXCHANGE is electrogenic and moves one net positive charge per cycle1,2. Although the cardiac exchanger has a three-to-one Na+/Ca2+ stoichiometry3, details of the reaction cycle are not well defined2,4–8. Here we associate Na+ translocation by the cardiac exchanger with positive charge movement in giant membrane patches from cardiac myocytes9,10 and oocytes expressing the cloned cardiac Na+/Ca2+ exchanger11. The charge movements are initiated by step increments of the cytoplasmic Na+ concentration in the absence of Ca2+. Giant patches from control oocytes lack both steady-state Na+/Ca2+ exchange current (INaCa) Na+-induced charge movements. Charge movements indicate about 400 exchangers per (μm2 in guinea-pig sarcolemma. Fully activated INaCa densities (20–30 μA cm–2) indicate maximum turnover rates of 5,000s−1. As has been predicted for consecutive exchange models4–7, the apparent ion affinities of steady stateINaCa increase as the counterion concentrations are decreased. Consistent with an electroneutral Ca2+ translocation, we find that voltage dependence of INaCa in both directions is lost as Ca2+ concentration is decreased. The principal electrogenic step seems to be at the extracellular end of the Na+ translocation pathway.

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Author notes

  1. Debora A. Nicoll and Kenneth D. Philipson: Departments of Medicine and Physiology and the Cardiovascular Research Laboratory, UCLA School of Medicine, Los Angeles, California 90024, USA

Affiliations

  1. Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 75235, USA

    • Donald W. Hilgemann
    • , Debora A. Nicoll
    •  & Kenneth D. Philipson

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https://doi.org/10.1038/352715a0

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