Low sodium inotropy is accompanied by diastolic Ca2+ gain and systolic loss in isolated guinea-pig ventricular myocytes.
We measured sarcolemmal Ca2+ fluxes responsible for the positive inotropic effects of solutions with reduced Na+ concentration in voltage-clamped guinea-pig ventricular myocytes; intracellular Ca2+ concentration ([Ca2+]i) was measured with Indo-1. Reduction of external Na+ concentration by 50 % (to 67 mM) produced an increase in systolic [Ca2+]i accompanied by a decrease in Ca2+ entry via the L-type Ca2+ current. With reduced Na+ concentration, there was an initial decrease in the Na+-Ca2+ exchange current on repolarization followed by an increase to greater than control. We attribute this initial decrease to a decrease in the Na+ gradient and the subsequent increase to a fall in intracellular Na+ concentration and increase in systolic [Ca2+]i. The decreased L-type Ca2+ current and increased Ca2+ efflux on Na+-Ca2+ exchange resulted in a calculated systolic loss of Ca2+. The calculated systolic loss of Ca2+ was accompanied by a measured increase in sarcoplasmic reticulum (SR) Ca2+ content. Reduction of the external Na+ concentration also produced an outward shift of holding current which was blocked by Ni2+. This is taken to represent Ca2+ influx via Na+-Ca2+ exchange. When diastolic influx is taken into account, the observed gain in SR Ca2+ content can be predicted. The measurements show that, in reduced Na+, much of the entry of Ca2+ into the cell occurs during diastole (via Na+-Ca2+ exchange) rather than in systole (via the L-type Ca2+ current).
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Unit of Cardiac Physiology, University of Manchester, 1.524 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
O'Neill
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Eisner
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D000818:Animals; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D003971:Diastole / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D008564:Membrane Potentials; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D012508:Sarcolemma / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013599:Systole / Q000502:physiology*
D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium