An opener of atp-sensitive k+ channels protects cardiomyocytes from
moderate hyperkalemia-induced ca2+ waves: a laser confocal microscopy
study.
L[acute]opez, Jos[acute]e R., R. A. Ghanbari, and Andre Terzic.
Division of Cardiovascular Diseases, Departments of Medicine and
Pharmacology
APStracts 2:0407H, 1995.
Laser confocal microscopy was used to visualize intracellular
spatiotemporal Ca2+ patterns in single guinea-pig ventricular
myocytes loaded with the Ca2+ indicator, Fluo-3, and exposed to
moderately elevated extracellular K+ in order to induce partial
membrane depolarization. Analysis of K+-induced intracellular Ca2+
elevation revealed three distinct paradigms: (1) diffuse, non
-oscillatory, Ca2+ elevation across the myocyte, (2) localized Ca2+
elevation in anatomically restricted areas (Ca2+ sparks), and (3)
regenerative frontal propagations of Ca2+ which 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 [mu]m/sec with an
average frequency of 1 wave per second crossing 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+ to induce Ca2+ waves. In
summary, moderate hyperkalemia induces distinct non-uniform patterns
of intracellular Ca2+ elevation in ventricular cells, which can be
prevented by a potassium channel opening drug through a glyburide
-sensitive mechanism.
Received 12 July 1995; accepted in final form 31 August 1995.
APS Manuscript Number H642-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.