抄録
Cardiac contraction is elicited by the release of stored Ca2+, following the opening of L-type Ca channels (L-Ch). We observe properties of Ca2+-induced Ca2+-release (CICR) as a result of averaged behavior of individual Ca-release unit (local control theory). Mathematical modeling of CICR thus requires stochastic simulations of numerous dyadic spaces, and is computationally highly demanding. The possible simplest formulation of local control is to treat Ca-release units as a distribution of four distinct states, where ryanodine receptors (RyR) open/close and L-Ch open/close. Based on the rapid equilibrium approximation of [Ca2+] between dyadic space and cytosol (Hinch, 2004), we developed a model of CICR where the distribution of Ca-release units over four states was estimated using macroscopic and/or single channel gating properties of L-Ch and RyR. We then incorporate it into a human ventricular action potential model (tenTusscher, 2004) with minor modifications. We tried several types of macroscopic L-Ch gating scheme obtained in a variety of experimental settings. Data on physiological RyR gating, in contrast, is scarce. We used a simple C-O-I Markov model and a popular four-states scheme (Stern, 1999; Bers' lab. 2004,2005). After tuning of RyR gating constants, models with different sets of RyR/L-Ch properties consistently reproduced essential features of CICR: (1)graded release, (2)experimentally observed voltage-dependence of EC-coupling gain. Being extensible to tissue levels, our model provides basis to investigate intracellular Ca2+ dynamics in wide physiological/pathological conditions. [J Physiol Sci. 2007;57 Suppl:S207]
