Arnaud Guilbert1, Hyun Joung Lim1, Jun Cheng2, Yanggan Wang3. 1. Department of Pediatrics, Emory University, Atlanta, USA. 2. Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, China; Department of Pediatrics, Emory University, Atlanta, USA. 3. Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, China; Department of Pediatrics, Emory University, Atlanta, USA. Electronic address: ygwang2013@163.com.
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. METHODS AND 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.
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. METHODS AND 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: Fernando A L Dias; Lori A Walker; Grace M Arteaga; John S Walker; Kalpana Vijayan; James R Peña; Yunbo Ke; Rosalvo T H Fogaca; Atsushi Sanbe; Jeffrey Robbins; Beata M Wolska Journal: J Mol Cell Cardiol Date: 2006-06-30 Impact factor: 5.000
Authors: Rashad J Belin; Marius P Sumandea; Tomoyoshi Kobayashi; Lori A Walker; Veronica L Rundell; Dalia Urboniene; Milana Yuzhakova; Stuart H Ruch; David L Geenen; R John Solaro; Pieter P de Tombe Journal: Am J Physiol Heart Circ Physiol Date: 2006-06-30 Impact factor: 4.733
Authors: R Sacha Bhatia; Jack V Tu; Douglas S Lee; Peter C Austin; Jiming Fang; Annick Haouzi; Yanyan Gong; Peter P Liu Journal: N Engl J Med Date: 2006-07-20 Impact factor: 91.245
Authors: Qiongling Wang; Ann P Quick; Shuyi Cao; Julia Reynolds; David Y Chiang; David Beavers; Na Li; Guoliang Wang; George G Rodney; Mark E Anderson; Xander H T Wehrens Journal: Circ Arrhythm Electrophysiol Date: 2018-04
Authors: Lorna J Daniels; Rachel S Wallace; Olivia M Nicholson; Genevieve A Wilson; Fiona J McDonald; Peter P Jones; J Chris Baldi; Regis R Lamberts; Jeffrey R Erickson Journal: Cardiovasc Diabetol Date: 2018-06-14 Impact factor: 9.951