Modeling Ca2+ currents and buffered diffusion of Ca2+ in human β-cells during voltage clamp experiments

Macroscopic Ca2+ currents of the human beta-cells were characterized using the Hodgkin-Huxley formalism. Expressions describing the Ca2+-dependent inactivation process of the L-type Ca2+ channels in terms of the concentration of Ca2+ were obtained. By coupling the modeled Ca2+ currents to a three-dimensional model of buffered diffusion of Ca2+, we simulated the Ca2+ transients formed in the immediate vicinity of the cell membrane during voltage clamp experiments performed in high buffering conditions. Our modeling approach allowed us to consider the distribution of the Ca2+ sources over the cell membrane. The effect of exogenous (EGTA) and endogenous Ca2+ buffers on the temporal course of the Ca2+ transients was evaluated. We show that despite the high Ca2+ buffering capacity, nanodomains are formed in the submembrane space, where a peak Ca2+ concentration between similar to 76 and 143 mu M was estimated from our simulations. In addition, the contribution of each Ca2+ current to the formation of the Ca2+ nanodomains was also addressed. Here we provide a general framework to incorporate the spatial aspects to the models of the pancreatic beta-cell, such as a more detailed and realistic description of Ca2+ dynamics in response to electrical activity in physiological conditions can be provided by future models. (C) 2015 Elsevier Inc. All rights reserved.