Internal free magnesium modulates the voltage dependence of contraction and Ca transient in rabbit ventricular myocytes

F. Chris Howarth, Allan J. Levi

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20 Citations (Scopus)

Abstract

We investigated the effect of altering internal free magnesium concentration (Mg(i)) on the contraction and Ca(i) transient of patch-clamped rabbit ventricular myocytes. Experiments were performed at 35°C cells were held at -40 mV to inactivate Na channels and T-type Ca channels, and at this potential (and in the absence of cyclic AMP) 'Ca-induced Ca release' is the primary trigger mechanism. Cells dialysed with a low Mg(i) (2.9 μM) had a large and fast phasic contraction and Ca(i) transient at positive potentials (+60, +80 mV). Cells dialysed with a high Mg(i) (7.1 mM) had a small or absent phasic contraction and Ca(i) transient at positive potentials. These effects were due to a change in free Mg(i), and not due to a change in [Mg.ATP]. In cells dialysed with a low Mg(i), application of Ca channel blockers (32 μM nifedipine with 10 μM D600) for a single beat abolished current through L-type Ca channels (I(Ca,L)); however, 53% of the Ca(i) transient was still elicited. Adding 5 mM Ni to Ca channel blockers abolished the remaining Ca(i) transient, indicating that (in the absence of I(Ca,L)) the transient might be triggered by reverse Na/Ca exchange. In cells dialysed with a high Mg(i), a single-beat switch to Ca channel blockers was sufficient alone to abolish the Ca(i) transient, indicating that under these conditions Ca entry via I(Ca,L) is the primary sarcoplasmic reticulum trigger mechanism. These results suggest that raised free Mg(i) might partially inhibit the activity of the Na/Ca exchange, or might limit its ability to trigger Ca release.

Original languageEnglish
Pages (from-to)687-698
Number of pages12
JournalPflugers Archiv European Journal of Physiology
Volume435
Issue number5
DOIs
Publication statusPublished - 1998
Externally publishedYes

Keywords

  • Excitation-contraction coupling
  • Intracellular magnesium
  • L-type Ca current
  • Na/Ca exchange
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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