Regulation of intracellular free Mg2+ and contraction in single adult mammalian cardiac myocytes

H. S. Silverman, F. Di Lisa, R. C. Hui, H. Miyata, S. J. Sollott, R. G. Hansford, E. G. Lakatta, M. D. Stern

Research output: Contribution to journalArticlepeer-review

Abstract

Studies in isolated cardiac myocytes have increased our understanding of intracellular Ca2+ regulation. Because less is known about Mg2+ regulation, adult rat ventricular myocytes were loaded with the Mg2+- sensitive fluorescent probe mag-indo 1, and changes in intracellular Mg2+ concentration ([Mg2+](i)) and cell length were examined under a variety of conditions. The fluorescent signal was calibrated intracellularly and found to differ slightly from that for the probe in solution. Roughly 40% of the signal was intramitochondrial; the remainder was localized in the cytosol. Basal [Mg2+](i) averaged 1.02 ± 0.03 mM (n = 53 cells). No change in [Mg2+](i) was observed during a single electrically stimulated contraction, and only a minor increase was seen during rapid electrical stimulation, which was expected to raise intracellular Ca2+ concentration ([Ca2+](i)) to ~1 μM. An acid shift in intracellular pH of ~1 pH unit was accompanied by a small change in [Mg2+](i) (0.34 ± 0.03 mM, n = 6, P < 0.05). No change in [Mg2+](i) was observed when cells were superfused with 15 mM Mg2+, despite marked changes in contraction. [Mg2+](i) more than doubled when cells were depleted of ATP by exposure to hypoxia or metabolic inhibitors. The increase in [Mg2+](i) was abrupt and occurred at the time of the failure of contraction, plateauing as rigor contracture developed. Reoxygenation was accompanied by a gradual fall in [Mg2+](i) in cells that recovered mechanical function, and in a subset of cells that underwent hypercontracture. Studies in cell suspensions confirmed that rapid cellular energy depletion was accompanied by increases in [Mg2+](i) and parallel decreases in ATP. Thus [Mg2+](i) was largely insensitive to changes in [Ca2+](i) or pH(i) and extracellular [Mg2+] but was rapidly altered by changes in energy state in a manner that was related to specific changes in cell morphology and contractile function.

Original languageEnglish (US)
Pages (from-to)C222-C233
JournalAmerican Journal of Physiology - Cell Physiology
Volume266
Issue number1 35-1
DOIs
StatePublished - 1994

Keywords

  • energetics
  • hypoxia
  • magnesium

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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