Sarcoplasmic reticulum Ca2+ ATPase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca2+ handling capacity

M. Jane Lalli, Ji Yong, Vikram Prasad, Katsuji Hashimoto, Dave Plank, Gopal J. Babu, Darryl Kirkpatrick, Richard A. Walsh, Mark Sussman, Atsuko Yatani, Eduardo Marbán, Muthu Periasamy

Research output: Contribution to journalArticle

Abstract

Ectopic expression of the sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA 1a hearts show increased rates of contraction/relaxation and enhanced Ca2+ transients; however, the cellular mechanisms underlying altered Ca2+ handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca2+ load measurements revealed that TG myocytes have significantly enhanced SR Ca2+ load. Confocal line-scan images of field-stimulated SR Ca2+ release showed an increased rate of Ca2+ removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by ≈30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca2+ current density was reduced by ≈50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca2+ transport and cardiac contractility.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
JournalCirculation Research
Volume89
Issue number2
StatePublished - Jul 20 2001
Externally publishedYes

Keywords

  • Ca load
  • Cauptake
  • Contractility
  • Gene herapy
  • Sparks
  • Transgenic

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Lalli, M. J., Yong, J., Prasad, V., Hashimoto, K., Plank, D., Babu, G. J., Kirkpatrick, D., Walsh, R. A., Sussman, M., Yatani, A., Marbán, E., & Periasamy, M. (2001). Sarcoplasmic reticulum Ca2+ ATPase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca2+ handling capacity. Circulation Research, 89(2), 160-167.