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

Biophys J. 2009 Apr 22;96(8):3126-39. doi: 10.1016/j.bpj.2009.01.029.

Abstract

We examined the ionic mechanisms mediating depolarization-induced spike activity in pancreatic beta-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 Ca(2+) dynamics in wild-type and Kv2.1 null mouse islets. The model contains an L-type Ca(2+) current, a "rapid" delayed-rectifier K(+) current, a small slowly-activated K(+) current, a Ca(2+)-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 Ca(2+) homeostasis, replicates beta-cell AP and Ca(2+) 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 Ca(2+) current, assessment of the role of rapid delayed-rectifier K(+) current, and Ca(2+)-activated K(+) currents, demonstrating the important roles of the Ca(2+)-pump and background currents in the APs and bursts. This model provides acceptable fits to voltage-clamp, AP, and Ca(2+) concentration data based on in silico analysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Adenosine Triphosphate / metabolism
  • Animals
  • 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

Substances

  • Calcium Channels, L-Type
  • Delayed Rectifier Potassium Channels
  • Kcnb1 protein, mouse
  • Potassium Channels, Voltage-Gated
  • Shab Potassium Channels
  • Tetraethylammonium
  • Adenosine Triphosphate
  • Sodium
  • Glucose
  • Potassium
  • Calcium