Phospholamban-deficient mouse ventricular myocytes exhibited accelerated relaxation, increased SR Ca2+ load, and enhanced local Ca2+ gradients compared to wild-type 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 et al. (Fri,) conducted a other in Phospholamban deficiency. Phospholamban deficiency (PLB-KO) vs. Wild-type (WT) was evaluated on Subcellular properties of intracellular Ca2+ transients. Phospholamban-deficient mouse ventricular myocytes exhibited accelerated relaxation, increased SR Ca2+ load, and enhanced local Ca2+ gradients compared to wild-type cells.