title: No direct effect of creatine phosphate on the cross-bridge cycle in cardiac myofibrils.
abstract: Creatine phosphate (CP) and creatine kinase (CK) are involved in the rapid resynthesis of ATP and thereby serve to stabilize ATP concentration and to maintain free ADP low inside cardiac muscle cells during contraction. Recently, it has been suggested from experiments in permeabilized multicellular preparations that CP/CK also regulate the kinetics of the actomyosin interaction (cross-bridge cycle) and may explain contractile dysfunction, for instance, during ischemia. However, the reported effects of CP/CK may be confounded by diffusion limitations in multicellular preparations in which inorganic phosphate (P(i)) and ADP may significantly accumulate during contraction. To test this hypothesis, we measured force production and the rates of force development (k (ACT) and k (TR)) in isolated cardiac myofibrils, in which rapid concentration changes of Ca(2+), CP/CK, and P(i) were imposed using a rapid perfusion change system. The results showed that CP/CK did not influence maximum force-generating capacity, whereas P(i) markedly reduced force and increased the rates of force development. No effects of CP/CK on the rates of force development were observed, consistent with the notion that CP/CK do not exert a direct effect on the actomyosin interaction.
authors.affiliation: Dipartimento di Scienze Fisiologiche, Università di Firenze, Viale Morgagni 63, 50134, Florence, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Piroddi
authors.forename: A
authors.initials: A
authors.lastname: Belus
authors.forename: S
authors.initials: S
authors.lastname: Eiras
authors.forename: C
authors.initials: C
authors.lastname: Tesi
authors.forename: J
authors.initials: J
authors.lastname: van der Velden
authors.forename: C
authors.initials: C
authors.lastname: Poggesi
authors.forename: G J M
authors.initials: GJ
authors.lastname: Stienen
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism*
chemical_list: D010710:Phosphates; D010725:Phosphocreatine; D000205:Actomyosin; D003402:Creatine Kinase; D002118:Calcium