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Open AccessArticle

Effect of Ion Concentration Changes in the Limited Extracellular Spaces on Sarcolemmal Ion Transport and Ca2+ Turnover in a Model of Human Ventricular Cardiomyocyte

1
Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno 62500, Czech Republic
2
Institute of Thermomechanics—Branch Brno, Academy of Science of the Czech Republic, Technická 2, Brno 61669, Czech Republic
3
EA4612 Neurocardiology, University Claude Bernard Lyon 1, 8 Ave Rockefeller, Lyon 69373 Cedex 08, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2013, 14(12), 24271-24292; https://doi.org/10.3390/ijms141224271
Received: 27 September 2013 / Revised: 12 November 2013 / Accepted: 19 November 2013 / Published: 13 December 2013
(This article belongs to the Special Issue Computational Modelling of Biological Membranes)
We have developed a computer model of human cardiac ventricular myocyte (CVM), including t-tubular and cleft spaces with the aim of evaluating the impact of accumulation-depletion of ions in restricted extracellular spaces on transmembrane ion transport and ionic homeostasis in human CVM. The model was based on available data from human CVMs. Under steady state, the effect of ion concentration changes in extracellular spaces on [Ca2+]i-transient was explored as a function of critical fractions of ion transporters in t-tubular membrane (not documented for human CVM). Depletion of Ca2+ and accumulation of K+ occurring in extracellular spaces slightly affected the transmembrane Ca2+ flux, but not the action potential duration (APD90). The [Ca2+]i-transient was reduced (by 2%–9%), depending on the stimulation frequency, the rate of ion exchange between t-tubules and clefts and fractions of ion-transfer proteins in the t-tubular membrane. Under non-steady state, the responses of the model to changes of stimulation frequency were analyzed. A sudden increase of frequency (1–2.5 Hz) caused a temporal decrease of [Ca2+] in both extracellular spaces, a reduction of [Ca2+]i-transient (by 15%) and APD90 (by 13 ms). The results reveal different effects of activity-related ion concentration changes in human cardiac t-tubules (steady-state effects) and intercellular clefts (transient effects) in the modulation of membrane ion transport and Ca2+ turnover. View Full-Text
Keywords: human heart; cardiac cell; t-tubule; intercellular clefts; calcium; ion transport; computer model human heart; cardiac cell; t-tubule; intercellular clefts; calcium; ion transport; computer model
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Hrabcová, D.; Pásek, M.; Šimurda, J.; Christé, G. Effect of Ion Concentration Changes in the Limited Extracellular Spaces on Sarcolemmal Ion Transport and Ca2+ Turnover in a Model of Human Ventricular Cardiomyocyte. Int. J. Mol. Sci. 2013, 14, 24271-24292.

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