Calcium waves driven by "sensitization" wave-fronts.
OBJECTIVE
Cellular Ca(2+) waves are understood as reaction-diffusion systems sustained by Ca(2+)-induced Ca(2+) release (CICR) from Ca(2+) stores. Given the recently discovered sensitization of Ca(2+) release channels (ryanodine receptors; RyRs) of the sarcoplasmic reticulum (SR) by luminal SR Ca(2+), waves could also be driven by RyR sensitization, mediated by SR overloading via Ca(2+) pump (SERCA), acting in tandem with CICR.


METHODS
Confocal imaging of the Ca(2+) indicator fluo-3 was combined with UV-flash photolysis of caged compounds and the whole-cell configuration of the patch clamp technique to carry out these experiments in isolated guinea pig ventricular cardiomyocytes.


RESULTS
Upon sudden slowing of the SERCA in cardiomyocytes with a photoreleased inhibitor, waves indeed decelerated immediately. No secondary changes of Ca(2+) signaling or SR Ca(2+) content due to SERCA inhibition were observed in the short time-frame of these experiments.


CONCLUSIONS
Our findings are consistent with Ca(2+) loading resulting in a zone of RyR 'sensitization' traveling within the SR, but inconsistent with CICR as the predominant mechanism driving the Ca(2+) waves. This alternative mode of RyR activation is essential to fully conceptualize cardiac arrhythmias triggered by spontaneous Ca(2+) release.
Keller
Markus
M
Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland.
Kao
Joseph P Y
JP
Egger
Marcel
M
Niggli
Ernst
E
D000814:Aniline Compounds; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D006168:Guinea Pigs; D006352:Heart Ventricles; D006873:Hydroquinones / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010648:Phenylacetates / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014466:Ultraviolet Rays; D014966:Xanthenes
D000814:Aniline Compounds; D006873:Hydroquinones; C104811:O-(2-nitromandelyloxycarbonyl)-2,5-di-(tert-butyl)hydroquinone; D010648:Phenylacetates; D019837:Ryanodine Receptor Calcium Release Channel; D014966:Xanthenes; C059715:Fluo-3; C019359:2,5-di-tert-butylhydroquinone; D002110:Caffeine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium