Regulatory role of phospholamban in the efficiency of cardiac sarcoplasmic reticulum Ca2+ transport

Summary, in English

Phospholamban is an inhibitor of the sarcoplasmic reticulum Ca²⁺ transport apparent affinity for Ca²⁺ in cardiac muscle. This inhibitory effect of phospholamban can be relieved through its phosphorylation or ablation. To better characterize the regulatory mechanism of phospholamban, we examined the initial rates of Ca²⁺-uptake and Ca²⁺-ATPase activity under identical conditions, using sarcoplasmic reticulum-enriched preparations from phospholamban-deficient and wild-type hearts. The apparent coupling ratio, calculated by dividing the initial rates of Ca²⁺ transport by ATP hydrolysis, appeared to increase with increasing [Ca²⁺] in wild-type hearts. However, in the phospholamban-deficient hearts, this ratio was constant, and it was similar to the value obtained at high [Ca²⁺] in wild-type hearts. Phosphorylation of phospholamban by the catalytic subunit of protein kinase A in wild-type sarcoplasmic reticulum also resulted in a constant value of the apparent ratio of Ca²⁺ transported per ATP hydrolyzed, which was similar to that present in phospholamban-deficient hearts. Thus, the inhibitory effects of dephosphorylated phospholamban involve decreases in the apparent affinity of sarcoplasmic reticulum Ca²⁺ transport for Ca²⁺ and the efficiency of this transport system at low [Ca²⁺], both leading to prolonged relaxation in myocytes.

• Författare: K. Frank; C. Tilgmann; T. R. Shannon; D. M. Bers; E. G. Kranias
• Publiceringsår: 2000-11-21
• Språk: Engelska
• Sidor: 14176-14182
• Publikation/Tidskrift/Serie: Biochemistry
• Volym: 39
• Issue: 46
• Länkar: http://dx.doi.org/10.1021/bi001049k
• Dokumenttyp: Artikel i tidskrift
• Förlag: The American Chemical Society (ACS)
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 0006-2960