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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • K. Frank
  • C. Tilgmann
  • T. R. Shannon
  • D. M. Bers
  • E. G. Kranias
Externa organisationer
  • University of Cincinnati
  • Loyola University Chicago
Originalspråkengelska
Sidor (från-till)14176-14182
Antal sidor7
TidskriftBiochemistry
Volym39
Utgivningsnummer46
StatusPublished - 2000 nov 21
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa