title: Regulation of fibre contraction in a rat model of myocardial ischemia.
abstract: BACKGROUND
  The changes in the actomyosin crossbridge cycle underlying altered contractility of the heart are not well described, despite their importance to devising rational treatment approaches.
  
  
  RESULTS
  A rat ischemia-reperfusion model was used to determine the transitions of the crossbridge cycle impacted during ischemia. Compared to perfused hearts, the maximum force per cross-sectional area and Ca(2+) sensitivity of fibers from ischemic hearts were both reduced. Muscle activation by photolytic release of Ca(2+) and ATP suggested that the altered contractility was best described as a reduction in the rate of activation of noncycling actomyosin crossbridges to activated, cycling states. More specifically, the apparent forward rate constant of the transition between the nonforce bearing A-M.ADP.Pi state and the bound, force bearing AM*.ADP.Pi state was reduced in ischemic fibers, suggesting that this transition is commensurate with initial crossbridge activation. These results suggested an alteration in the relationship between the activation of thin filament regulatory units and initial crossbridge attachment, prompting an examination of the post-translational state of troponin (Tn) T and I. These analyses indicated a reduction in the diphosphorylated form of TnT during ischemia, along with lower Ser23/24 phosphorylation of TnI. Treatment of perfused fibers by 8-Br-cAMP increased Ser23/24 phosphorylation of TnI, altering the reverse rate constant of the Pi isomerization in a manner consistent with the lusitropic effect of beta-adrenergic stimulation. However, similar treatment of ischemic fibers did not change TnI phosphorylation or the kinetics of the Pi isomerization.
  
  
  CONCLUSIONS
  Ischemia reduces the isomerization from A-M.ADP.Pi to AM*.ADP.Pi, altering the kinetics of crossbridge activation through a mechanism that may be mediated by altered TnT and TnI phosphorylation.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Han
authors.forename: Ozgur
authors.initials: O
authors.lastname: Ogut
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry; D004195:Disease Models, Animal; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000473:pathology*; D018994:Myosin Light Chains / Q000737:chemistry; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000737:chemistry; D020107:Troponin T / Q000737:chemistry; D000099163:Myosin Binding Protein C
chemical_list: D002118:Calcium; D002352:Carrier Proteins; D018994:Myosin Light Chains; D019210:Troponin I; D020107:Troponin T; D000099163:Myosin Binding Protein C