Subcellular properties of [Ca2+]i transients in phospholamban-deficient mouse ventricular cells.
The regulatory protein phospholamban exerts a physiological inhibitory effect on the sarcoplasmic reticulum (SR) Ca2+ pump that is relieved with phosphorylation. We have studied the subcellular properties of intracellular Ca2+ ([Ca2+]i) transients in ventricular myocytes isolated from wild-type (WT) and phospholamban-deficient (PLB-KO) mice. In PLB-KO myocytes, steady-state twitch [Ca2+]i transients revealed an accelerated relaxation and the occurrence of highly localized failures of Ca2+ release. The acceleration of SR Ca2+ uptake caused an increase in SR Ca2+ load with the frequent occurrence of spontaneous [Ca2+]i waves and Ca2+ sparks. [Ca2+]i waves in PLB-KO cells showed a marked decrease in spatial width and more frequently appeared to abort. Local Ca2+ release events (Ca2+ sparks) were larger and more variable in amplitude and [Ca2+]i declined faster in PLB-KO myocytes. Increased local buffering and reduction in the refractoriness of SR Ca2+ release caused by the increased SR pump rate led to an overall enhancement of local [Ca2+]i gradients and inhomogeneities in the [Ca2+]i distribution during spontaneous Ca2+ release, [Ca2+]i waves, and excitation-contraction coupling.
Hüser
J
J
Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Bers
D M
DM
Blatter
L A
LA
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D002478:Cells, Cultured; D004594:Electrophysiology; D017136:Ion Transport / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016276:Ventricular Function; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000099211:Phospholamban