title: Protein kinase A changes calcium sensitivity but not crossbridge kinetics in human cardiac myofibrils.
abstract: We investigated the effect of PKA treatment (1 U/ml) on the mechanical properties of isolated human cardiac myofibrils. PKA treatment was associated with significant incorporation of radiolabeled phosphate into several sarcomeric proteins including troponin I and myosin binding protein C and was also associated with a right shift in the tension-pCa relation (ΔpCa(50) = 0.2 ± 0.1). PKA treatment also caused right shifts in the pCa dependence of the rate of tension development, tension redevelopment, and the linear and exponential phases of myofibril relaxation. However, there was no change in the same measures of crossbridge turnover when expressed as a function of tension. We conclude that the changes in crossbridge kinetics as a function of calcium concentration reflect a reduced tension due to a lower calcium sensitivity and that the relationship between crossbridge kinetics and tension was unchanged, indicating no direct effect of PKA treatment on crossbridge cycling.
authors.affiliation: Division of Cardiology, Dept. of Medicine, Univ. of Colorado, Denver, Aurora CO 80045, USA. john.s.walker@ucdenver.edu
authors.forename: John S
authors.initials: JS
authors.lastname: Walker
authors.forename: Lori A
authors.initials: LA
authors.lastname: Walker
authors.forename: Ken
authors.initials: K
authors.lastname: Margulies
authors.forename: Peter
authors.initials: P
authors.lastname: Buttrick
authors.forename: Pieter
authors.initials: P
authors.lastname: de Tombe
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D002021:Buffers; D020013:Calcium Signaling / Q000187:drug effects*; D002314:Cardioplegic Solutions; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000648:ultrastructure; D009210:Myofibrils / Q000187:drug effects* / Q000648:ultrastructure; D010761:Phosphorus Radioisotopes; D012518:Sarcomeres / Q000187:drug effects / Q000648:ultrastructure; D055815:Young Adult
chemical_list: D002021:Buffers; D002314:Cardioplegic Solutions; D010761:Phosphorus Radioisotopes; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases