Premium
Transmural variation in myosin heavy chain isoform expression modulates the timing of myocardial force generation in porcine left ventricle
Author(s) -
Stelzer Julian E.,
Norman Holly S.,
Chen Peter P.,
Patel Jitandrakumar R.,
Moss Richard L.
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.160390
Subject(s) - myofilament , ventricle , myosin , gene isoform , medicine , cardiology , chemistry , myofibril , anatomy , biophysics , biology , biochemistry , gene
Recent studies have shown that the sequence and timing of mechanical activation of myocardium vary across the ventricular wall. However, the contributions of variable expression of myofilament protein isoforms in mediating the timing of myocardial activation in ventricular systole are not well understood. To assess the functional consequences of transmural differences in myofilament protein expression, we studied the dynamic mechanical properties of multicellular skinned preparations isolated from the sub‐endocardial and sub‐epicardial regions of the porcine ventricular midwall. Compared to endocardial fibres, epicardial fibres exhibited significantly faster rates of stretch activation and force redevelopment ( k tr ), although the amount of force produced at a given [Ca 2+ ] was not significantly different. Consistent with these results, SDS‐PAGE analysis revealed significantly elevated expression of α myosin heavy chain (MHC) isoform in epicardial fibres (13 ± 1%) versus endocardial fibres (3 ± 1%). Linear regression analysis revealed that the apparent rates of delayed force development and force decay following stretch correlated with MHC isoform expression ( r 2 = 0.80 and r 2 = 0.73, respectively, P < 0.05). No differences in the relative abundance or phosphorylation status of other myofilament proteins were detected. These data show that transmural differences in MHC isoform expression contribute to regional differences in dynamic mechanical function of porcine left ventricles, which in turn modulate the timing of force generation across the ventricular wall and work production during systole.