The role of Na+-Ca2+ exchange in activation of excitation-contraction coupling in rat ventricular myocytes

J. Andrew Wasserstrom*, Ana Maria Vites

*Corresponding author for this work

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

1. The purpose of this study was to determine whether mechanisms other than Ca2+ influx via L-type Ca2+ current (ICa) might contribute to activation of contraction in rat ventricular myocytes. The whole-cell voltage-clamp technique was used with normal transmembrane K+ and Na+ gradients at 34 °C. The sarcoplasmic reticulum (SR) was conditioned with one to three prepulses to +100 mV for 100 ms. 2. Cell shortening (ΔL) increased with test voltage up to a plateau level at about +20 mV, beyond which cell shortening remained fairly constant, thus describing a sigmoidal voltage dependence. This relationship was obtained when holding potential (Vh) was either -40 or -70 mV; however, greater shortening was obtained at the more negative Fh. 3. The sigmoidal V-ΔL, relationship was converted to a bell shape following the magnitude of ICa when internal Cs+ was substituted for K+ and when the temperature was reduced to 22 °C. 4. At 34 °C, block of ICa with nifedipine (10 μM) decreased shortening by about 50% but did not alter the voltage dependence of ΔL/ when Fh was either -40 or -70 mV. Addition of Ni2+ (4-5 mM) blocked all remaining contractions. 5. When cell shortening was triggered by an action potential voltage clamp, there was again about 50% of the contraction that was insensitive to nifedipine but was blocked by Ni2+. 6. Our results demonstrate that there is a significant contribution of a nifedipine-insensitive mechanism to the activation of contraction. This mechanism is likely to be reverse mode Na+-Ca2+ exchange since it appears to be sensitive to both voltage and Ni2+. We conclude that a contribution of reverse Na+-Ca2+ exchange to activation of excitation-contraction coupling occurs in rat heart at near-physiological conditions which include warm temperatures, normal transmembrane Na+ and K+ gradients and activation in response to an action potential.

Original languageEnglish (US)
Pages (from-to)529-542
Number of pages14
JournalJournal of Physiology
Volume493
Issue number2
DOIs
StatePublished - Jun 1 1996

ASJC Scopus subject areas

  • Physiology

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