%0 Journal Article %1 Szen_2004_807 %A Szentesi, Peter %A Pignier, Christophe %A Egger, Marcel %A Kranias, Evangelia G %A Niggli, Ernst %D 2004 %J Circ. Res. %K 15388639 ATPase, Acetic Acids, Animals, Caffeine, Calcium Calcium, Calcium-Binding Cardiac, Channel Channel, Contraction, Ethylenediamines, Exchanger, Gating, Gov't, Guinea Indoles, Ion Isoproterenol, Knockout, Mice, Myocardial Myocardium, Myocytes, Non-P.H.S., Non-U.S. P.H.S., Patch-Clamp Photolysis, Pigs, Proteins, Rays, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Signaling, Sodium-Calcium Support, Techniques, U.S. Ultraviolet {C}a$^{2+}$-Transporting %N 8 %P 807--813 %R 10.1161/01.RES.0000146029.80463.7d %T Sarcoplasmic reticulum Ca$^2+$ refilling controls recovery from Ca$^2+$-induced Ca$^2+$ release refractoriness in heart muscle. %U http://dx.doi.org/10.1161/01.RES.0000146029.80463.7d %V 95 %X In cardiac muscle Ca$^2+$-induced Ca$^2+$ release (CICR) from the sarcoplasmic reticulum (SR) is initiated by Ca$^2+$ influx via L-type Ca$^2+$ channels. At present, the mechanisms underlying termination of SR Ca$^2+$ release, which are required to ensure stable excitation-contraction coupling cycles, are not precisely known. However, the same mechanism leading to refractoriness of SR Ca$^2+$ release could also be responsible for the termination of CICR. To examine the refractoriness of SR Ca$^2+$ release, we analyzed Na$^+$-Ca$^2+$ exchange currents reflecting cytosolic Ca$^2+$ signals induced by UV-laser flash-photolysis of caged Ca$^2+$. Pairs of UV flashes were applied at various intervals to examine the time course of recovery from CICR refractoriness. In cardiomyocytes isolated from guinea-pigs and mice, beta-adrenergic stimulation with isoproterenol-accelerated recovery from refractoriness by approximately 2-fold. Application of cyclopiazonic acid at moderate concentrations (<10 micromol/L) slowed down recovery from refractoriness in a dose-dependent manner. Compared with cells from wild-type littermates, those from phospholamban knockout (PLB-KO) mice exhibited almost 5-fold accelerated recovery from refractoriness. Our results suggest that SR Ca$^2+$ refilling mediated by the SR Ca$^2+$-pump corresponds to the rate-limiting step for recovery from CICR refractoriness. Thus, the Ca$^2+$ sensitivity of CICR appears to be regulated by SR Ca$^2+$ content, possibly resulting from a change in the steady-state Ca$^2+$ sensitivity and in the gating kinetics of the SR Ca$^2+$ release channels (ryanodine receptors). During Ca$^2+$ release, the concomitant reduction in Ca$^2+$ sensitivity of the ryanodine receptors might also underlie Ca$^2+$ spark termination by deactivation.

@article{Szen_2004_807, abstract = {In cardiac muscle {C}a$^{2+}$-induced {C}a$^{2+}$ release (CICR) from the sarcoplasmic reticulum (SR) is initiated by {C}a$^{2+}$ influx via L-type {C}a$^{2+}$ channels. At present, the mechanisms underlying termination of SR {C}a$^{2+}$ release, which are required to ensure stable excitation-contraction coupling cycles, are not precisely known. However, the same mechanism leading to refractoriness of SR {C}a$^{2+}$ release could also be responsible for the termination of CICR. To examine the refractoriness of SR {C}a$^{2+}$ release, we analyzed {N}a$^{+}$-{C}a$^{2+}$ exchange currents reflecting cytosolic {C}a$^{2+}$ signals induced by UV-laser flash-photolysis of caged {C}a$^{2+}$. Pairs of UV flashes were applied at various intervals to examine the time course of recovery from CICR refractoriness. In cardiomyocytes isolated from guinea-pigs and mice, beta-adrenergic stimulation with isoproterenol-accelerated recovery from refractoriness by approximately 2-fold. Application of cyclopiazonic acid at moderate concentrations (<10 micromol/L) slowed down recovery from refractoriness in a dose-dependent manner. Compared with cells from wild-type littermates, those from phospholamban knockout (PLB-KO) mice exhibited almost 5-fold accelerated recovery from refractoriness. Our results suggest that SR {C}a$^{2+}$ refilling mediated by the SR {C}a$^{2+}$-pump corresponds to the rate-limiting step for recovery from CICR refractoriness. Thus, the {C}a$^{2+}$ sensitivity of CICR appears to be regulated by SR {C}a$^{2+}$ content, possibly resulting from a change in the steady-state {C}a$^{2+}$ sensitivity and in the gating kinetics of the SR {C}a$^{2+}$ release channels (ryanodine receptors). During {C}a$^{2+}$ release, the concomitant reduction in {C}a$^{2+}$ sensitivity of the ryanodine receptors might also underlie {C}a$^{2+}$ spark termination by deactivation.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Szentesi, Peter and Pignier, Christophe and Egger, Marcel and Kranias, Evangelia G and Niggli, Ernst}, biburl = {https://www.bibsonomy.org/bibtex/22ec15b39059b848334fbc8229df53c88/hake}, description = {The whole bibliography file I use.}, doi = {10.1161/01.RES.0000146029.80463.7d}, file = {Szen_2004_807.pdf:Szen_2004_807.pdf:PDF}, interhash = {99a0f290ebe19814a88232968a1d7fb8}, intrahash = {2ec15b39059b848334fbc8229df53c88}, journal = {Circ. Res.}, key = 233, keywords = {15388639 ATPase, Acetic Acids, Animals, Caffeine, Calcium Calcium, Calcium-Binding Cardiac, Channel Channel, Contraction, Ethylenediamines, Exchanger, Gating, Gov't, Guinea Indoles, Ion Isoproterenol, Knockout, Mice, Myocardial Myocardium, Myocytes, Non-P.H.S., Non-U.S. P.H.S., Patch-Clamp Photolysis, Pigs, Proteins, Rays, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Signaling, Sodium-Calcium Support, Techniques, U.S. Ultraviolet {C}a$^{2+}$-Transporting}, month = Oct, number = 8, pages = {807--813}, pii = {01.RES.0000146029.80463.7d}, pmid = {15388639}, timestamp = {2009-06-03T11:21:33.000+0200}, title = {Sarcoplasmic reticulum {C}a$^{2+}$ refilling controls recovery from {C}a$^{2+}$-induced {C}a$^{2+}$ release refractoriness in heart muscle.}, url = {http://dx.doi.org/10.1161/01.RES.0000146029.80463.7d}, volume = 95, year = 2004 }