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

• Published in: Biophysical journal 2009-04, Vol.96 (8), p.3126-3139
• Main Authors: Fridlyand, L.E., Jacobson, D.A., Kuznetsov, A., Philipson, L.H.
• Format: Article
• Language: English
• Subjects: Action Potentials; Adenosine Triphosphate - metabolism; Animals; Biophysical Theory and Modeling; Calcium - metabolism; Calcium Channels, L-Type - metabolism; Calcium Signaling; Cell Membrane - physiology; Computer Simulation; Delayed Rectifier Potassium Channels - metabolism; Glucose - metabolism; Insulin-Secreting Cells - physiology; Mice; Mice, Knockout; Models, Neurological; Patch-Clamp Techniques; Potassium - metabolism; Potassium Channels, Voltage-Gated - antagonists & inhibitors; Shab Potassium Channels - genetics; Sodium - metabolism; Tetraethylammonium - pharmacology; Time
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2009.01.029

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.