Na/Ca exchange function in intact ventricular myocytes

Abstract

Here, we address three issues in intact ventricular myocytes that specifically relate to the role of Na/Ca exchange (NCX) current under physiological conditions. First, we revisit the issue of NCX stoichiometry in light of some recent findings that the stoichiometry of the NCX may not be fixed at 3Na: 1Ca. We discuss some data that strongly favor the 3:1 stoichiometry, at least under physiological conditions. Second, we address the controversy over the role of allosteric Ca regulation in intact myocytes. We show that outward and inward I(NCX) can be activated dynamically by changing [Ca](i) over the physiological range and that outward I(NCX) can be activated quite rapidly with sarcoplasmic reticulum Ca release. These data are well described using an instantaneous equation for NCX current that includes an allosteric activation factor with K(mCaAct) = 125 nM. Finally, we consider the effect on NCX current of submembrane elevations in [Ca](i) (that are far greater than are measured in the bulk cytoplasm). Taken together with a NCX stoichiometry of 3, these findings have allowed us to make some predictions of the role of I(NCX) during an AP. Our simulations suggest that NCX current is outward for less than approximately 10 ms at the beginning of the action potential.