title: Cell-to-cell variability in troponin I phosphorylation in a porcine model of pacing-induced heart failure.
abstract: We tested the hypothesis that myocardial contractile protein phosphorylation and the Ca(2+) sensitivity of force production are dysregulated in a porcine model of pacing-induced heart failure (HF). The level of protein kinase A (PKA)-dependent cardiac troponin I (TnI) phosphorylation was lower in the myocardium surrounding the pacing electrode (pacing site) of the failing left ventricle (LV) than in the controls. Immunohistochemical assays of the LV pacing site pointed to isolated clusters of cardiomyocytes exhibiting a reduced level of phosphorylated TnI. Flow cytometry on isolated and permeabilized cardiomyocytes revealed a significantly larger cell-to-cell variation in the level of TnI phosphorylation of the LV pacing site than in the opposite region in HF or in either region in the controls: the interquartile range (IQR) on the distribution histogram of relative TnI phosphorylation was wider at the pacing site (IQR = 0.53) than that at the remote site of HF (IQR = 0.42; P = 0.0047) or that of the free wall of the control animals (IQR = 0.36; P = 0.0093). Additionally, the Ca(2+) sensitivities of isometric force production were higher and appeared to be more variable in single permeabilized cardiomyocytes from the HF pacing site than in the healthy myocardium. In conclusion, the level of PKA-dependent TnI phosphorylation and the Ca(2+) sensitivity of force production exhibited a high cell-to-cell variability at the LV pacing site, possibly explaining the abnormalities of the regional myocardial contractile function in a porcine model of pacing-induced HF.
authors.affiliation: Division of Clinical Physiology, Research Center for Molecular Medicine, Institute of Cardiology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
authors.forename: Dániel
authors.initials: D
authors.lastname: Czuriga
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
authors.forename: Eniko T
authors.initials: ET
authors.lastname: Pásztor
authors.forename: Agnes
authors.initials: A
authors.lastname: Balogh
authors.forename: Andrea
authors.initials: A
authors.lastname: Bodnár
authors.forename: Eniko
authors.initials: E
authors.lastname: Nizsalóczki
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
authors.forename: István
authors.initials: I
authors.lastname: Czuriga
authors.forename: István
authors.initials: I
authors.lastname: Edes
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Papp
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002304:Cardiac Pacing, Artificial; D002469:Cell Separation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006333:Heart Failure / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009210:Myofibrils / Q000378:metabolism*; D010766:Phosphorylation; D013552:Swine; D019210:Troponin I / Q000378:metabolism*
chemical_list: D019210:Troponin I