Can Ca entry via Na-Ca exchange directly activate cardiac muscle contraction?

Donald M Bers, David M. Christensen, Trung X. Nguyen

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Developed twitch tension and action potentials were recorded in rabbit ventricular muscle in physiological saline at 30°C stimulated at 0.5 Hz. Addition of 5 μm nifedipine to block Ca entry via Ca channels almost abolished twitches (to 2.5±0.7%, s.e.m., n=10 of control). This suggests that under normal conditions Ca entry via Na-Ca exchange is insufficient to activate contractions. However, when muscles are first exposed to 4 μm acetyl-strophanthidin to elevate [Na]i the same exposure to nifedipine only partially suppresses twitches (to 59±12% of the original control). This suggests that when [Na]i is elevated, Ca entry via the Na-Ca exchange may be adequate to partially activate contraction. From this result it is not clear whether Ca entry via Na-Ca exchange is sufficient to activate contraction directly or whether sarcoplasmic reticulum (SR) Ca release is required. When these experiments were carried out in the presence of 5 to 10 mm caffeine or 100 nm ryanodine similar results were obtained. That is, nifedipine still abolished contractions in the presence of caffeine or ryanodine (to 3.8±0.3% and 1.3±0.4%, respectively), but only partially inhibited contractions in the presence of caffeine + acetylstrophanthidin (to 21±5%) or ryanodine + acetylstrophanthidin (10±2%). Thus, it appears that even in the absence of a functional SR and with Ca current blocked, Na-Ca exchange might bring sufficient Ca into the cell to activate appreciable contractions, but only when [Na]i is elevated. Action potential duration is decreased by nifedipine and acetylstrophanthidin and is further decreased when nifedipine is added on top of acetylstrophanthidin. If this Ca entry is by an electrogenic 3 Na: 1 Ca exchange, Ca entry will be favored at more positive membrane potentials. If the action potential were not so abbreviated with these drugs, Na-Ca exchange might bring in more Ca and activate additional tension.

Original languageEnglish (US)
Pages (from-to)405-414
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume20
Issue number5
DOIs
StatePublished - 1988

Keywords

  • Acetylstrophanthidin
  • Caffeine
  • Excitation-contraction coupling
  • Nifedipine
  • Rabbit ventricle
  • Ryanodine

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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