Phospholamban Decreases the Energetic Efficiency of the Sarcoplasmic Reticulum Ca Pump

Thomas R. Shannon, Guoxiang Chu, Evangelia G. Kranias, Donald M Bers

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

We tested the hypothesis that increased Sarcoplasmic reticulum (SR) Ca content ([Ca]SRT) in phospholamban knockout mice (PLB-KO) is because of increased SR Ca pump efficiency defined by the steady-state SR [Ca] gradient. The time course of thapsigargin-sensitive ATP-dependent 45Ca influx into and efflux out of cardiac SR vesicles from PLB-KO and wild-type (WT) mice was measured at 100 nM free [Ca]. We found that PLB decreased the initial SR Ca uptake rate (0.13 versus 0.31 nmol/mg/s) and decreased steady-state 45Ca content (0.9 versus 4.1 nmol/mg protein). Furthermore, at similar total SR [Ca], the pump-mediated Ca efflux rate was higher in WT (0.065 versus 0.037 nmol/mgts). The pump-independent leak rate constant (k leak) was also measured at 100 nM free [Ca]. The results indicate that kleak was < 1% of pump-mediated backflux and was not different among nonpentameric mutant PLB (PLB-C41F), WT pentameric PLB (same expression level), and PLB-KO. Therefore differences in passive SR Ca leak cannot be the cause of the higher thapsigargin-sensitive Ca efflux from the WT membranes. We conclude that the decreased total SR [Ca] in WT mice is caused by decreased SR Ca influx rate, an increased Ca-pump backflux, and unaltered leak. Based upon both thermodynamic and kinetic analysis, we conclude that PLB decreases the energetic efficiency of the SR Ca pump.

Original languageEnglish (US)
Pages (from-to)7195-7201
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number10
DOIs
StatePublished - Mar 9 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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