AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 274: H1800-H1811, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 5, H1800-H1811, May 1998

Subcellular properties of [Ca2+]i transients in phospholamban-deficient mouse ventricular cells

Jörg Hüser, Donald M. Bers, and Lothar A. Blatter

Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153

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.

confocal microscopy; sarcoplasmic reticulum; calcium sparks; intracellular calcium waves; excitation-contraction coupling


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