Modeling Ca(2+) currents and buffered diffusion of Ca(2+) in human β-cells during voltage clamp experiments

Macroscopic Ca(2+) currents of the human β-cells were characterized using the Hodgkin-Huxley formalism. Expressions describing the Ca(2+)-dependent inactivation process of the L-type Ca(2+) channels in terms of the concentration of Ca(2+) were obtained. By coupling the modeled Ca(2+) currents to a three-dimensional model of buffered diffusion of Ca(2+), we simulated the Ca(2+) 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 Ca(2+) sources over the cell membrane. The effect of exogenous (EGTA) and endogenous Ca(2+) buffers on the temporal course of the Ca(2+) transients was evaluated. We show that despite the high Ca(2+) buffering capacity, nanodomains are formed in the submembrane space, where a peak Ca(2+) concentration between ∼76 and 143 µM was estimated from our simulations. In addition, the contribution of each Ca(2+) current to the formation of the Ca(2+) nanodomains was also addressed. Here we provide a general framework to incorporate the spatial aspects to the models of the pancreatic β-cell, such as a more detailed and realistic description of Ca(2+) dynamics in response to electrical activity in physiological conditions can be provided by future models.