Na-Ca Countertransport in Cardiac Muscle

  • Harald Reuter


The discovery of Na-Ca countertransport across cell membranes involved three major steps:
  1. 1.

    Wilbrandt and Koller (1948) and Lüttgau and Niedergerke (1958) suggested that Ca2+ and Na+ ions compete for anionic groups at the membrane surface, either by distributing themselves according to a Dornnan equilibrium (Wilbrandt and Koller, 1948) or by interacting more specifically with these groups (Lüttgau and Niedergerke, 1958). In each case, formation of a Ca-anion complex was assumed to be somehow responsible for activation of contraction of the frog heart. Application of the law of mass action predicted that the Ca-anion complex, and hence contraction, should depend on the ratio [Ca2+]: [Na+]2 in the external medium. This prediction fitted the experimental data reasonably well. Both hypotheses also implied that Ca adsorption to surface membranes, and/or Ca uptake into intact tissues, should be inversely proportional to the external Na+ concentration. This has been confirmed by various investigators (Niedergerke, 1963; Langer, 1964; Baker and Blaustein, 1968). This Na-Ca antagonism, however, could not account for Na-Ca countertransport across the membrane.

  2. 2.

    On the basis of 45Ca flux measurement in guinea pig atria, Reuter and Seitz (1967, 1968) found that not only does Ca influx depend on external Na, but also Ca efflux. They suggested that a Na-Ca heteroexchange diffusion system exists in cardiac cell membranes that controls the intracellular Ca concentration. In such a “carrier-mediated” transport system, the downhill movement of Na+ (or Ca2+) ions can provide the free energy for uphill movement of Ca2+ (or Na+) ions across the membrane. The original hypothesis of a Na-Ca countertransport system (Reuter and Seitz, 1968) suggested an electroneutral exchange of 2 Na+ for 1 Ca2+. The stoichiometry is under debate, but the basic concept of Na-Ca exchange has been confirmed by many studies in heart and other tissues (for reviews see Baker, 1972; Reuter, 1974; Blaustein, 1974; Mullins, 1976; Sulakhe and St. Louis, 1980).



Cardiac Muscle Squid Axon Frog Heart Sarcolemmal Vesicle Uphill Movement 
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Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Harald Reuter
    • 1
  1. 1.Department of PharmacologyUniversity of BernBernSwitzerland

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