Preprint Article Version 1 This version is not peer-reviewed

The Effects of Load on Transmural Differences in Contraction of Isolated Mouse Ventricular Cardiomyocytes

Version 1 : Received: 12 December 2016 / Approved: 13 December 2016 / Online: 13 December 2016 (09:49:15 CET)

How to cite: Khokhlova, A.; Iribe, G.; Katsnelson, L.; Naruse, K.; Solovyova, O. The Effects of Load on Transmural Differences in Contraction of Isolated Mouse Ventricular Cardiomyocytes. Preprints 2016, 2016120066 (doi: 10.20944/preprints201612.0066.v1). Khokhlova, A.; Iribe, G.; Katsnelson, L.; Naruse, K.; Solovyova, O. The Effects of Load on Transmural Differences in Contraction of Isolated Mouse Ventricular Cardiomyocytes. Preprints 2016, 2016120066 (doi: 10.20944/preprints201612.0066.v1).

Abstract

Mechanical properties of cardiomyocytes from different transmural regions are heterogeneous in the left ventricular wall. The cardiomyocyte mechanical environment affects this heterogeneity because of mechano-electric feedback mechanisms. In the present study, we investigated the effects of load upon transmural differences in contraction of subendocardial (ENDO) and subepicardial (EPI) single cells isolated from the murine left ventricle. Various loads were applied to the cells using carbon fiber techniques for single myocytes. To simulate experimentally obtained results and to predict mechanisms underlying the cellular response to change in load, our mathematical models of the ENDO and EPI cells were used. Extent of the transmural gradient in the time course of contractions was independent of the loading conditions where unloaded and heavy loaded (isometric) contractions were examined, but the regional gradient of the relaxation time characteristics tended to decrease when the load decreased. Under auxotonic contractions, time to peak contraction (Tmax) was significantly longer in ENDO cells than in EPI cells at low preload. An increase in preload (axial stretch) prolonged Tmax in both cell types; however, the prolongation was greater in EPI cells, resulting in a decrease in transmural gradient in Tmax at high preload. The [Ca2+]i transient decay time constant was consistent with the greater preload dependency in Tmax of EPI cells. Our modified mathematical models reproduced experimental results, suggesting that differences in cooperativity of cross bridges and calcium troponin C complex interactions between the ENDO and EPI cardiomyocytes may contribute to the different cellular responses to stretch, which may provide a decrease in transmural dispersion of cellular shortening in the intact heart.

Subject Areas

ventricular transmural heterogeneity; cellular mechanics; load dependency; calcium transient; mechano-calcium feedback

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