A Population Density Domain Model for Calcium-Inactivation of L-Type Calcium Channels

Abstract

We present a minimal whole cell model of stochastic domain Ca-mediated inactivation of low-density L-type Ca channels. Our approach avoids the computationally demanding task of resolving spatial aspects of global Ca signaling by using probability densities and associated moment equations to represent heterogeneous local Ca signals [Williams et al. Biophys J. 92(7):2311-28, 2007; Biophys J. 95(4):1689-703, 2008]. using a minimal Markov chain model of an L-type Ca channel, simulated whole cell responses to a two-pulse voltage clamp protocol yield an inactivation function for the whole cell Ca current that is similar to - but may deviate from - that obtained by assuming instantaneous formation and collapse of Ca domains [Sherman, Keizer, Rinzel. Biophys J. 58(4):985-95, 1990]. Parameter studies reveal that when domain Ca formation and collapse are slow compared to channel kinetics (e.g., fast voltage-dependent gating), the population density description is required to accurately represent the dynamics of Ca inactivation of whole cell L-type currents. When channel kinetics are slow, the population density approach agrees with - and thus generalizes - “instantaneous domain” models of Ca inactivation.