Low sodium inotropy is accompanied by diastolic Ca2+ gain and systolic loss in isolated guinea-pig ventricular myocytes

J Physiol. 2001 Feb 1;530(Pt 3):487-95. doi: 10.1111/j.1469-7793.2001.0487k.x.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / physiology*
  • Calcium Channels, L-Type / physiology*
  • Cell Membrane / physiology
  • Cells, Cultured
  • Diastole / physiology
  • Guinea Pigs
  • Heart / drug effects
  • Heart / physiology*
  • Heart Ventricles
  • Membrane Potentials
  • Myocardial Contraction
  • Myocardium / cytology
  • Patch-Clamp Techniques
  • Sarcolemma / metabolism
  • Sarcoplasmic Reticulum / metabolism
  • Sodium / pharmacology
  • Sodium / physiology*
  • Sodium-Calcium Exchanger / metabolism
  • Systole / physiology*

Substances

  • Calcium Channels, L-Type
  • Sodium-Calcium Exchanger
  • Sodium
  • Calcium