Interaction between increased SERCA2a activity and β-adrenoceptor stimulation in adult rabbit myocytes

Babar Chaudhri, Federica Del Monte, Roger J. Hajjar, Sian E. Harding

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a overexpression and phospholamban depletion have been shown to have beneficial effects on contractility in heart failure. However, the high sympathetic tone during development of failure may interact with increases in SERCA2a activity in potentially deleterious ways. We used adenoviral vectors to overexpress SERCA2a or partially downregulate phospholamban in adult rabbit ventricular myocytes in culture and studied the responses of these cells to β-adrenoceptor stimulation. SERCA2a overexpression and phospholamban depletion had quantitatively similar effects on basal contraction amplitude and in accelerating relaxation. Increasing SERCA2a activity by either strategy had little effect on the increase in contraction amplitude or incidence of arrhythmias with increasing isoproterenol. Maximum acceleration of relaxation by β-adrenoceptor stimulation was similar to that produced by SERCA2a overexpression. Isoproterenol treatment of SERCA2a-overexpressing or phospholamban-deficient myocytes produced a further modest decrease in relaxation time, with similar final values in both groups. We find no evidence for Ca2+ overload induced by SERCA2a overexpression alone or in combination with catecholamines.

Original languageEnglish
Pages (from-to)H2450-H2457
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number6 52-6
DOIs
StatePublished - 1 Dec 2002
Externally publishedYes

Keywords

  • Aftercontraction
  • Antisense
  • Arrhythmia
  • Phospholamban

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