Analysis of Ion Concentration Changes in Transverse Axial Tubular System in a Model of Human Ventricular Cardiomyocyte

Dana Ohlídalová, Michal Pásek*, Jiří Šimurda

Department of Physiology, Faculty of Medicine, Masaryk University, Brno

*pasek.avcr@centrum.cz

The cardiac transverse-axial tubular system (TATS) is a complex network of membrane invaginations. Both structural and functional studies have suggested that the TATS constitutes a region that is highly specialised for excitation-contraction coupling because many of the key proteins involved in transmembrane Ca²⁺ flux appear to be located predominantly in the TATS (Orchard et al., 2009). In this paper, we present a model of human ventricular cardiomyocyte incorporating TATS and the results of quantitative analysis of ion concentration changes in tubular lumen at different stimulation rates.

A model originally proposed to explore the TATS properties in guinea-pig ventricular myocyte (Pásek et al., 2008) was adopted and modified to meet the recently published results of electrophysiological experiments on isolated human cardiomyocytes (e. g.Gui-Rong et al. 1998).

Fig. 1. Steady state intracellular Ca²⁺-transients ([Ca²⁺]_i) under presence (red dotted line) and absence (solid blue line) of ion concentration changes in TATS during 3 Hz stimulation.

Exploration of activity-dependent changes in tubular ion concentrations revealed a  relative Ca²⁺ depletions of about 8 % in the range of stimulation frequencies 1-3 Hz. Meanwile, as the stimulation rate increased the relative maximum accumulation of tubular K⁺ decreased from 1.7 % to 0.7 %. The relative changes of tubular Na⁺ were negligible. The preliminary analysis of the effects of tubular Ca²⁺ depletion indicates its role in limitation of intracellular Ca²⁺ overload (Fig. 1). The detailed exploration of physiological consequences of this phenomenon is the subject of our further investigation.

References

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Pásek M,Šimurda J, Orchard C, Christé G. A model of the guinea-pig ventricular cardiac myocyte incorporating a transverse-axial tubular system. Progress Biophys and Mol Biol, 96: 258 – 280, 2008

Gui-Rong L, Feng J, Yue L, Carrier M. Transmural heterogenity of action potentials and Ito1 in myocytes isolated from the human right ventricle. Am J Physiol Heart Circ Physiol, 275: 369 – 377, 1998