Modelling the Electrical Activity of Pancreatic α-cells Based on Experimental Data from Intact Mouse Islets

Abstract

Detailed experimental data from patch clamp experiments on pancreatic α-cells in intact mouse islets are used to model the electrical activity associated with glucagon secretion. Our model incorporates L- and T-type Ca²⁺ currents, delayed rectifying and A-type K⁺ currents, a voltage-gated Na⁺ current, a KATP conductance, and an unspecific leak current. Tolbutamide closes KATP channels in the α-cell, leading to a reduction of the resting conductance from 1.1 nS to 0.4 nS. This causes the α-cell to depolarise from −76 mV to 33 mV. When the basal membrane potential passes the range between −60 and −35 mV, the α-cell generates action potentials. At higher voltages, the α-cell enters a stable depolarised state and the electrical activity ceases. The effects of tolbutamide are simulated by gradually reducing the KATP conductance (g _K,ATP ) from 500 pS to 0 pS. When g _K,ATP is between 72 nS and 303 nS, the model generates action potentials in the same voltage range as the α-cell. When g _K,ATP is lower than 72 nS, the model enters a stable depolarised state, and firing of action potentials is inhibited due to voltage-dependent inactivation of the Na⁺ and T-type Ca²⁺ currents. This is in accordance with experimental results. Changing the inactivation parameters to those observed in somatostatin-secreting δ-cells abolishes the depolarised inactive state, and leads to β-cell like electrical activity with action potentials generated even after complete closure of the KATP channels.