A KATP channel opener protects cardiomyocytes from Ca2+ waves: a laser confocal microscopy study.
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.
López
J R
JR
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Ghanbari
R A
RA
Terzic
A
A
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D007425:Intracellular Membranes / Q000378:metabolism; D018613:Microscopy, Confocal; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010847:Picolines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology*
D010847:Picolines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011714:Pyrans; C061043:aprikalim; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide; D002118:Calcium