title: Protein kinase A-mediated acceleration of the stretch activation response in murine skinned myocardium is eliminated by ablation of cMyBP-C.
abstract: Beta-adrenergic agonists induce protein kinase A (PKA) phosphorylation of the cardiac myofilament proteins myosin binding protein C (cMyBP-C) and troponin I (cTnI), resulting in enhanced systolic function, but the relative contributions of cMyBP-C and cTnI to augmented contractility are not known. To investigate possible roles of cMyBP-C in this response, we examined the effects of PKA treatment on the rate of force redevelopment and the stretch activation response in skinned ventricular myocardium from both wild-type (WT) and cMyBP-C null (cMyBP-C(-/-)) myocardium. In WT myocardium, PKA treatment accelerated the rate of force redevelopment and the stretch activation response, resulting in a shorter time to the peak of delayed force development when the muscle was stretched to a new isometric length. Ablation of cMyBP-C accelerated the rate of force redevelopment and stretch activation response to a degree similar to that observed in PKA treatment of WT myocardium; however, PKA treatment had no effect on the rate of force development and the stretch activation response in null myocardium. These results indicate that ablation of cMyBP-C and PKA treatment of WT myocardium have similar effects on cross-bridge cycling kinetics and suggest that PKA phosphorylation of cMyBP-C accelerates the rate of force generation and thereby contributes to the accelerated twitch kinetics observed in living myocardium during beta-adrenergic stimulation.
authors.affiliation: Department of Physiology, University of Wisconsin Medical School, 1300 University Ave, Madison, WI 53706, USA. stelzer@physiology.wisc.edu
authors.forename: Julian E
authors.initials: JE
authors.lastname: Stelzer
authors.forename: Jitandrakumar R
authors.initials: JR
authors.lastname: Patel
authors.forename: Richard L
authors.initials: RL
authors.lastname: Moss
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology*; D006321:Heart / Q000502:physiology*; D006652:Histological Techniques; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D013314:Stress, Mechanical; D013997:Time Factors; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D000099163:Myosin Binding Protein C