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A MODIFIED MATHEMATICAL MODEL OF HUMAN VENTRICULAR CARDIOMYOCYTE INCORPORATING SEPARATE T-TUBULAR AND SURFACE DYADS AND SUBMEMBRANE SPACES
Pásek, Michal ; Bébarová, M. ; Christé, G.
Intracellular Ca2+ load and Ca2+ transient are considerably dependent on distribution of sarcolemmal Ca2+ pump and Na+-Ca2+ exchanger between the t-tubular and surface membranes in the presence of separate dyadic and subsarcolemmal spaces in rat ventricular cell model. To explore analogical phenomenon in human, we modified our previously published model of human ventricular myocyte. When the t-tubular fractions of Na+-Ca2+ exchanger and of sarcolemmal Ca2+ pump were increased to the newly proposed value of 0.95 in the modified model, the following changes were observed at 1 Hz steady-state stimulation: a shortening of the action potential duration at 90% repolarisation by 6% and an increase of the cytosolic Ca2+ transient by 22%. Further analysis revealed a critical role of Ca2+ concentration changes in the subsarcolemmal spaces and consequent change in cellular Ca2+ cycling in this effect.
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Sensitivity of action potential to changes of inward rectifier potassium current IK1 is different in recent models of human ventricular cardiomyocytes
Pásek, Michal ; Šimurda, J. ; Christé, G.
The inwardly rectifying potassium current IK1 is one of the principle ionic currents responsible for repolarization phase of mammalian action potentials (APs). To estimate the impact of individual ionic currents on AP configuration, mathematical models have been widely used. In this study, we compared the effects of alcohol-induced changes of IK1 on AP duration (APD) as simulated in four recently published computer models of human ventricular cells. As expected, increasing or decreasing IK1 conductance by 20% respectively caused a shortening or a lengthening of APD. However, the effect was largely model-dependent, ranging from 1% to about 15% change of APD. Given the conflicting available experimental data on the features of IK1 in human ventricular myocytes there is a need for a set of well-established end-point constraints for a reliable human ventricular myocyte model to be generated.
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Physiological consequences of ion concentration changes in transverse-axial tubular system in a model of human ventricular cardiomyocyte
Ohlidalova, D. ; Pásek, Michal ; Šimurda, J. ; Christé, G.
A mathematical model of human ventricular cell incorporating the transverse axial tubular system (TATS) was designed and used to explore the role of TATS in human ventricular cell electrophysiological activity. The model is based on the latest quantitative description of guinea pig ventricular cell electrophysiology and modified to respect the published data obtained from human cardiac preparations. Computer simulations suggest that significant transient depletions of Ca2+ ions and accumulation of K+ ions may occur in the human TATS. The preliminary analysis of the effects of tubular Ca2+depletions on the activity of the model cell indicates their role in limitation of intracellular Ca2+ overload at higher frequencies of stimulation.
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Inženýrská mechanika
Fuis, Vladimír ; Pásek, Michal
The objective of the 14 th conference is to provide a forum for researchers to discuss the state-of-the-art in Mechanics of Solids, Fluids and Thermomechanics, this particularly in connection with problems under investigation in the Czech Republic.
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Blokáda sodíkového a přechodného draslíkového proudu perfenazinem: experimentální a simulační studie
Bébarová, M. ; Matejovič, P. ; Pásek, Michal ; Jansová, D. ; Šimurdová, M. ; Nováková, M. ; Šimurda, J.
The effect of a neuroleptic drug perphenazine on sodium current INa and transient outward potassium current Ito was studied in rat ventricular myocytes at room temperature. Perphenazine reversibly blocked INa (reducing its amplitude; IC50 = 1.24 +/- 0.10 μmol/l, nH =0.99 +/- 0.08) and Ito (accelerating its apparent inactivation with a slight decrease of its amplitude; IC50 = 38.2 +/- 3.5 μmol/l, nH = 0.75 +/- 0.07, evaluated from the changes of time integral). Both INa- and Ito-block was use- and frequency-dependent (20%-increase of INablock and 10%-increase of Ito-block under 0.3 and 10 μmol/l perphenazine, respectively, at the stimulation frequency of 3.3 Hz applied after a 15-s rest). The results of quantitative modelling suggest that perphenazine interacts with INa-channels in inactivated states, and with Ito-channels in both open and open-inactivated states.
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Využití MKP pro analýzu netradičního chlazení servo pohu
Vlach, Radek ; Pásek, Michal ; Grepl, Robert ; Krejčí, Petr
This project is concerned with non-convectional servo machine cooling using heat pipe. The aim was created computational model using finite elements method. The thermal model was built in software ANSYS 11. The thermal model using finite elements method was used for the check of such cooling. The aim was to examine the possibilities of using heat pipe for cooling of servo. The servo is possible overloaded using heat pipe, because heat pipe effectively reduces heating of machine.
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Využití matematického modelu pro odhad frakční plochy tubulární membrány u srdečních komorových buněk.
Pásek, Michal ; Šimurda, J.
The transverse (t-) tubules of cardiac ventricular myocytes create a complex network of membrane invaginations. Many of the key proteins involved in excitation-contraction coupling appear to be located predominantly at the t-tubule membrane. Despite their importance, the fraction of cell membrane within the t-tubules remains unclear: for example, measurement of cell capacitance following detubulation in rat cardiomyocytes suggests 32%, whereas optical measurements suggest up to 65%. We have therefore investigated the factors that may account for this discrepancy. Calculation of the combinations of t-tubule radius, length and density that produce t-tubular membrane fractions of 32% or 56% suggest that the true fraction is at the upper end of this range.
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Účinek perphenazinu na přechodný draslíkový proud u komorových buněk potkana
Bébarová, M. ; Matejovič, P. ; Pásek, Michal ; Račkauskas, G. ; Šimurdová, M. ; Šimurda, J. ; Nováková, M.
The aim of this study was to explore the effect of a phenothiazine neuroleptic drug perphenazine on transient outward potassium current Ito in rat ventricular myocytes. Perphenazine reversibly decreased the amplitude and accelerated the apparent inactivation of Ito in a concentration-dependent manner with EC50 = 26.4 +/- 3.5 µmol/l and Hill coefficient n = 0.84 +/- 0.10 (evaluated from changes of time integral of Ito). Time course of Ito-inactivation was well fitted by a double exponential function; the fast time constant was significantly decreased under the effect of perphenazine and its concentration dependence was comparable with the concentration dependence of Ito-block represented by time integrals (EC50 = 26.8 +/- 8.2 µmol/l, n = 0.88 +/- 0.28). It is suggested that perphenazine-induced block via open channel is very likely involved in the mechanism of drug-channel interaction.
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