Creatine phosphate consumption and the actomyosin crossbridge cycle in cardiac muscles

Ozgur Ogut, Frank V. Brozovich

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

To investigate the regulation of the actomyosin crossbridge cycle in cardiac muscles, the effects of ATP, ADP, Pi, and creatine phosphate (CP) on the rate of force redevelopment (ktr) were measured. We report that CP is a primary determinant in controlling the actomyosin crossbridge cycling kinetics of cardiac muscles, because a reduction of CP from 25 to 2.5 mmol/L decreased ktr by 51% despite the presence of 5 mmol/L MgATP. The effects of CP on ktr were not a reflection of reduced ATP or accumulated ADP, because lowering ATP to 1 mmol/L or increasing ADP to 1 mmol/L did not significantly decrease ktr. Therefore, the effect of CP on the actomyosin crossbridge cycle is proposed to occur through a functional link between ADP release from myosin and its rephosphorylation by CP-creatine kinase to regenerate ATP. In activated fibers, the functional link influenced the kinetics of activated crossbridges without affecting the aggregate number of force-generating crossbridges. This was demonstrated by the ability of CP to affect ktr in maximally and submaximally activated fibers without altering the force per cross-sectional area. The data also confirm the important contribution of strong binding crossbridges to cardiac muscle activation, likely mediated by cooperative recruitment of adjacent crossbridges to maximize force redevelopment against external load. These data provide additional insight into the role of CP during pathophysiological conditions such as ischemia, suggesting that decreased CP may serve as a primary determinant in the observed decline of dP/dt.

Original languageEnglish (US)
Pages (from-to)54-60
Number of pages7
JournalCirculation research
Volume93
Issue number1
DOIs
StatePublished - Jul 11 2003

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Keywords

  • Actomyosin
  • Cardiac muscle
  • Creatine phosphate
  • Crossbridge cycle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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