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

Frank, K.; Tilgmann, C. LU ; Shannon, T. R.; Bers, D. M. and Kranias, E. G. (2000) In Biochemistry 39(46). p.14176-14182
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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
in
Biochemistry
volume
39
issue
46
pages
7 pages
publisher
The American Chemical Society
external identifiers
  • Scopus:0034700256
ISSN
0006-2960
DOI
10.1021/bi001049k
language
English
LU publication?
no
id
b1d4e674-9b77-4425-a496-40193a14b5f7
date added to LUP
2016-04-11 13:16:28
date last changed
2016-07-27 10:47:47
@misc{b1d4e674-9b77-4425-a496-40193a14b5f7,
  abstract     = {<p>Phospholamban is an inhibitor of the sarcoplasmic reticulum Ca<sup>2+</sup> transport apparent affinity for Ca<sup>2+</sup> 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 Ca<sup>2+</sup>-uptake and Ca<sup>2+</sup>-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 Ca<sup>2+</sup> transport by ATP hydrolysis, appeared to increase with increasing [Ca<sup>2+</sup>] in wild-type hearts. However, in the phospholamban-deficient hearts, this ratio was constant, and it was similar to the value obtained at high [Ca<sup>2+</sup>] 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> transport for Ca<sup>2+</sup> and the efficiency of this transport system at low [Ca<sup>2+</sup>], both leading to prolonged relaxation in myocytes.</p>},
  author       = {Frank, K. and Tilgmann, C. and Shannon, T. R. and Bers, D. M. and Kranias, E. G.},
  issn         = {0006-2960},
  language     = {eng},
  month        = {11},
  number       = {46},
  pages        = {14176--14182},
  publisher    = {ARRAY(0xb5c33a8)},
  series       = {Biochemistry},
  title        = {Regulatory role of phospholamban in the efficiency of cardiac sarcoplasmic reticulum Ca2+ transport},
  url          = {http://dx.doi.org/10.1021/bi001049k},
  volume       = {39},
  year         = {2000},
}