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This Article Full Text Full Text (PDF) All Versions of this Article: 586/21/5203    most recent jphysiol.2008.160390v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Stelzer, J. E. Articles by Moss, R. L. PubMed PubMed Citation Articles by Stelzer, J. E. Articles by Moss, R. L. Related Collections Cardiovascular

¹ Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA

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 [Ca²⁺] was not significantly different. Consistent with these results, SDS-PAGE analysis revealed significantly elevated expression of 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 (r² = 0.80 and r² = 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.

(Received 23 July 2008; accepted after revision 11 September 2008; first published online 11 September 2008)
Corresponding author J. E. Stelzer: Department of Physiology, University of Wisconsin School of Medicine and Public Health, 601 Science Drive, Madison, WI 53711, USA. Email: stelzer{at}physiology.wisc.edu