Abstract
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.
Highlights
The increased availability of experimental data obtained from human isolated cardiomyocytes in recent years provided sufficient material to mathematically describe the transmembrane ion transport and electrical activity in human atrial [1,2] and ventricular cells [3,4,5,6,7,8]
Because the values of some parameters that are related to the features of t-tubules in human ventricular myocytes are still unknown, we explored the physiological consequences of their various combinations, in particular those related to cellular electro-mechanical activity
This study demonstrates that ion concentration changes in the t-system of human cardiomyocytes, though small compared to those observed in skeletal muscle [23,24], are not negligible and should be considered in a detailed description of a human ventricular myocyte as a factor contributing to the control of Ca2+ turnover and cardiac contraction
Summary
The increased availability of experimental data obtained from human isolated cardiomyocytes in recent years provided sufficient material to mathematically describe the transmembrane ion transport and electrical activity in human atrial [1,2] and ventricular cells [3,4,5,6,7,8]. None of these models, included a description of the effects of simultaneous changes of ion concentrations in the intercellular cleft space and t-tubular system as functional compartments that may affect cellular activity.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
