title: CaMKII-dependent myofilament Ca2+ desensitization contributes to the frequency-dependent acceleration of relaxation.
abstract: BACKGROUND
  Previous studies suggest that CaMKII activity is required for frequency-dependent acceleration of relaxation (FDAR) in ventricular myocytes. We propose that the underlying mechanism involves CaMKII-dependent regulation of myofilament Ca(2+) sensitivity.
  
  
  RESULTS
  Cardiac function was measured in mice using murine echo machine. [Ca(2+)]i and sarcomere length were measured by IonOptix Ca(2+) image system. Increasing pacing rate from 0.5 to 4 Hz in left ventricular myocytes induced frequency-dependent myofilament Ca(2+) desensitization (FDMCD) and FDAR. Acute inhibition of PKA or PKC had no effect, whereas CaMKII inhibition abolished both FDMCD and FDAR. Co-immunoprecipitation of CaMKII and troponin I (TnI) has been detected and CaMKII inhibition significantly reduced serine residue phosphorylation of TnI. Finally, chronic inhibition of CaMKII in vivo reduced TnI phosphorylation and abolished both FDAR and FDMCD, leading to impaired diastolic function.
  
  
  CONCLUSIONS
  Our results suggest that CaMKII-dependent TnI phosphorylation is involved in FDMCD and the consequent FDAR and that CaMKII inhibition removes this mechanism and thus induces diastolic dysfunction.
authors: Department of Pediatrics, Emory University, Atlanta, USA.
authors: Arnaud
authors: A
authors: Guilbert
authors: Department of Pediatrics, Emory University, Atlanta, USA.
authors: Hyun Joung
authors: HJ
authors: Lim
authors: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, China; Department of Pediatrics, Emory University, Atlanta, USA.
authors: Jun
authors: J
authors: Cheng
authors: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, China; Department of Pediatrics, Emory University, Atlanta, USA. Electronic address: ygwang2013@163.com.
authors: Yanggan
authors: Y
authors: Wang
mesh_terms: D000054:Acceleration; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009210:Myofibrils / Q000378:metabolism*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517671:Camk2a protein, mouse; D002118:Calcium
keywords: CaMKII; Contraction; Myocytes; Myofilament Ca(2+) sensitivity; Relaxation