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

Electrophysiological models of the human pancreatic δ‐cell: From single channels to the firing of action potentials

“…According to these values, we estimate a range of 21 to 66 T‐type Ca 2+ channels in the human δ‐cell, which yields a density of 0.05 and 0.15 channels per μm 2 . Given that the experimental I‐V curve of the T‐type current was not reported by Braun et al, the simulated I‐V curve shown in Figure F was estimated from the experimental I‐V curve of the T‐type current in human β‐cells shown in the same figure. The simulated I‐V curve showed a maximal current of approximately 12 pA for a voltage pulse of −30 mV, as reported in human β‐cells, being also consistent with the experimental observations in human δ‐cells of a depolarizing pulse from −70 to −30 mV (fig.…”

“…For the I KA current, we used the average values of the activation and inactivation time constants reported by Braun et al; that is, millisecond and milliseconds. The activation time constant of the L‐type Ca 2+ current and inactivation time constants of the T‐type Ca 2+ current and the voltage dependent Na + currents were estimated from the values reported in previous models of currents of human β‐cells (ie, τ mL = 1.25 ms, τ hT = 15 ms, τ Na = 2 ms) . For the I Kdr current, the time constants were modelled as a voltage‐dependent function, adopting the function obtained from the analysis of experimental data from human β‐cells (see Section 3.3).…”

“…The activation time constant of the L-type Ca 2+ current and inactivation time constants of the T-type Ca 2+ current and the voltage dependent Na + currents were estimated from the values reported in previous models of currents of human β-cells (ie, τ mL = 1.25 ms, τ hT = 15 ms, τ Na = 2 ms). [26][27][28]31 For the I Kdr current, the time constants were modelled as a voltage-dependent function, adopting the function obtained from the analysis of experimental data from human β-cells (see Section 3.3). Experimental recordings of the macroscopic I Kdr currents showed a faster activation as the magnitude of the depolarized pulse increased, as was also observed in human β-cells (see fig.…”

“…Given the now known importance of paracrine signaling within the islets of Langerhans, mathematical modeling has been used to study the electrophysiological behavior of endocrine islet cells and the interactions between them within the pancreatic islets (see, for instance, Watts et al and Briant et al). It should be noted, however, that most of the models have been based on data from rodent cells, while only a few of them have been developed to describe the electrical activity of human β‐cells . While a model of the human α‐cell is still lacking, here, we present the first model of the electrical activity of the human δ‐cell.…”

“…It should be noted, however, that most of the models have been based on data from rodent cells, while only a few of them have been developed to describe the electrical activity of human β-cells. 19,[26][27][28][29] While a model of the human α-cell is still lacking, here, we present the first model of the electrical activity of the human δ-cell. Specifically, in this work, we aim to develop mathematical models capable of reproducing both the macroscopic currents and the action potentials generated in response to a glucose stimulus in human δ-cells based in the experimental work by Braun et al 1 2 | METHODOLOGY…”