A Model of Action Potentials and Fast Ca2+ Dynamics in Pancreatic β-Cells

Abstract

We examined the ionic mechanisms mediating depolarization-induced spike activity in pancreatic β-cells. We formulated a Hodgkin-Huxley-type ionic model for the action potential (AP) in these cells based on voltage- and current-clamp results together with measurements of Ca2+ dynamics in wild-type and Kv2.1 null mouse islets. The model contains an L-type Ca2+ current, a “rapid” delayed-rectifier K+ current, a small slowly-activated K+ current, a Ca2+-activated K+ current, an ATP-sensitive K+ current, a plasma membrane calcium-pump current and a Na+ background current. This model, coupled with an equation describing intracellular Ca2+ homeostasis, replicates β-cell AP and Ca2+ changes during one glucose-induced spontaneous spike, the effects of blocking K+ currents with different inhibitors, and specific complex spike in mouse islets lacking Kv2.1 channels. The currents with voltage-independent gating variables can also be responsible for burst behavior. Original features of this model include new equations for L-type Ca2+ current, assessment of the role of rapid delayed-rectifier K+ current, and Ca2+-activated K+ currents, demonstrating the important roles of the Ca2+-pump and background currents in the APs and bursts. This model provides acceptable fits to voltage-clamp, AP, and Ca2+ concentration data based on in silico analysis.