Impact of T-tubules on electrical activity of cardiac cells evaluated in a quantitative model

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Authors

PÁSEK Michal CHRISTÉ Georges ŠIMURDA Jiří

Year of publication 2003
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description We report here the first quantitative evaluation of the role of the transverse-axial tubular (TAT) system in the electrical activity of cardiac cells. Our approach uses a biophysically-based representation of the TAT-system incorporated into a model of cardiac ventricular cell (Jafri et al., Biophys. J. 1998, 74:1149-68). The model was modified to agree more closely with recent published data. The differential distribution of ion transfer mechanisms in peripheral and tubular membranes was included (e.g. K+ channels; Christé, J. Mol. Cell. Cardiol. 1999, 31:2207-13). Changes of ion concentrations in the TAT-lumen were computed from the total transmembrane ion fluxes and ion exchanges with the pericellular medium. Long term stability of the model was verified at rest and under regular stimulation, the charge conservation principle being respected. The tubular membrane voltage during an action potential was nearly identical with the peripheral membrane voltage, indicating that propagation of excitation along the TAT-system was quasi-instantaneous. Depletion of Ca2+ by 12.8 % and accumulation of K+ by 4.7 % occurred in the TAT-lumen during the course of an action potential at 1 Hz. However, the course of action potential was only slightly altered when the TAT-system was included into the model (shortening by less than 2 % at 90 % of repolarization). Under conditions of progressive hypokalaemia, the TAT-system retarded the occurrence of delayed after-depolarizations owing principally to Ca2+ depletion in the TAT-system and subsequently to suppression of Ca2+ overload in sarcoplasmic reticulum. They occurred at more severe hypokalaemia. These results show that modulation of the excitation-contraction coupling of ventricular cardiac tissue formerly attributed rather to narrow extracellular spaces is also an intrinsic property of the ventricular cardiac myocyte TAT-system, where the preferential localization of ion transfer mechanisms plays a key role.
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