AJP - Heart and Circulatory Physiology, Vol 270, Issue 4 1384-H1389, Copyright © 1996 by American Physiological Society

ARTICLES

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

J. R. Lopez, R. A. Ghanbari and A. Terzic
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.

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 approximately 60 microns/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 form patterns of intracellular Ca2+ elevation in ventricular cells, which can be prevented by a potassium channel-opening drug through a glyburide-sensitive mechanism.

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