A model of action potentials and fast Ca2+ dynamics in pancreatic beta-cells.

Fridlyand LE, Jacobson DA, Kuznetsov A, Philipson LH
Biophys J. 2009 96 (8): 3126-39

PMID: 19383458 · PMCID: PMC2718303 · DOI:10.1016/j.bpj.2009.01.029

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.

MeSH Terms (21)

Action Potentials Adenosine Triphosphate Animals Calcium Calcium Channels, L-Type Calcium Signaling Cell Membrane Computer Simulation Delayed Rectifier Potassium Channels Glucose Insulin-Secreting Cells Mice Mice, Knockout Models, Neurological Patch-Clamp Techniques Potassium Potassium Channels, Voltage-Gated Shab Potassium Channels Sodium Tetraethylammonium Time

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