Modelling the electrical activity of pancreatic alpha-cells based on experimental data from intact mouse islets

Paul Matthias Diderichsen, S.O. Gopel

Research output: Contribution to journalJournal articlepeer-review

Abstract

Detailed experimental data from patch clamp experiments on pancreatic alpha-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 alpha-cell, leading to a reduction of the resting conductance from 1.1 nS to 0.4 nS. This causes the alpha-cell to depolarise from -76 mV to 33 mV. When the basal membrane potential passes the range between -60 and -35 mV, the alpha-cell generates action potentials. At higher voltages, the alpha-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 alpha-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 delta-cells abolishes the depolarised inactive state, and leads to beta-cell like electrical activity with action potentials generated even after complete closure of the KATP channels.
Original languageEnglish
JournalJournal of Biological Physics
Volume32
Issue number3-4
Pages (from-to)209-229
ISSN0092-0606
Publication statusPublished - 2006

Keywords

  • inactivation
  • membrane potential
  • pancreatic alpha-cell
  • glucagon
  • ion channel

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