A KATP channel opener protects cardiomyocytes from Ca2+ waves: A laser confocal microscopy study

José R. López, R. A. Ghanbari, Andre Terzic

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Laser confocal microscopy was used to visualize intracellular spatiotemporal Ca2+ patterns in single guinea pig ventricular myocytes loaded with the Ca2+ indicator, fluo 3-acetoxymethyl ester (fluo 3-AM), and exposed to moderately elevated extracellular K+ to induce partial membrane depolarization. Analysis of K+-induced intracellular Ca2+ elevation revealed three distinct paradigms: 1) diffuse, nonoscillatory Ca2+ elevation across the myocyte; 2) localized Ca2+ elevation in anatomically restricted areas (Ca2+ sparks); and 3) regenerative frontal propagations of Ca2+ that traversed the length of the cell (Ca2+ waves). The first two patterns were more frequently observed when the extracellular K+ concentration was raised to 8 mM. Ca2+ waves became more common when extracellular K+ concentration was increased to 16 mM, suggesting that a minimum threshold of increase in intracellular Ca2+ is necessary for the organization of Ca2+ waves. The velocity of propagation was typically ∼60 μm/s with an average frequency of one wave per second crossing at a given point in the cell. Wave propagation resulted in spatial and temporal oscillations in cytosolic and nuclear Ca2+ concentration. Treating cardiac cells with aprikalim, a potassium channel-opening drug, prevented 16 mM K+ (but not 32 mM K+) from inducing an increase in Ca2+ concentration and from generating Ca2+ waves. In cardiomyocytes treated with glyburide, a selective antagonist of ATP-sensitive K channels, aprikalim failed to prevent 16 mM K+ from inducing Ca2+ waves. In summary, moderate hyperkalemia induces distinct nonuniform patterns of intracellular Ca2+ elevation in ventricular cells, which can be prevented by a potassium channel-opening drug through a glyburide-sensitive mechanism.

Original languageEnglish (US)
Pages (from-to)H1384-H1389
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume270
Issue number4 39-4
DOIs
StatePublished - Jan 1 1996

Keywords

  • ATP-sensitive K channel
  • Calcium wave
  • Cardiac cell
  • Hyperkalemia
  • Laser confocal microscopy
  • Potassium channel opener

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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