Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts

Taurine is a beta-amino acid found in very high concentration in the heart. Depletion of these intracellular stores results in the development of cardiomyopathy, thought to be mediated by abnormal sarcoplasmic reticular (SR) Ca2+ transport. There is also evidence that taurine directly alters the Ca2+ sensitivity of myofibrillar proteins. Major regulators of SR Ca2+ ATPase (SERCA2a) are the phosphorylation status of a regulatory protein, phospholamban, and SERCA2a expression, which are diminished in the failing heart. The failing heart also exhibits reductions in myofibrillar Ca2+ sensitivity, a property regulated by the phosphorylation of the muscle protein, troponin I. Therefore, we tested the hypothesis that taurine deficiency leads to alterations in SR Ca2+ ATPase activity related to reduced phospholamban phosphorylation and expression of SERCA2a. We found that a sequence of events, which included elevated protein phosphatase 1 activity, reduced autophosphorylation of CaMKII, and reduced phospholamban phosphorylation, supports the reduction in SR Ca2+ ATPase activity. However, the reduction in SR Ca2+ ATPase activity was not caused by reduced SERCA2a expression. Taurine transporter knockout (TauTKO) hearts also exhibited a rightward shift in the Ca2+ dependence of the myofibrillar Ca2+ ATPase, a property that is associated with an elevation in phosphorylated troponin I. The findings support the observation that taurine deficient hearts develop systolic and diastolic defects related to reduced SR Ca2+ ATPase activity, a change mediated in part by reduced phospholamban phosphorylation.