Effect of voltage-gated plasma membrane Ca2+ fluxes on IP3-linked Ca2+ oscillations.
We present a theoretical investigation of the effect of Ca2+ influx through ion channels in the plasma membrane on Ca2+ oscillations induced by agonist stimulation of Ca2+ release from internal stores. We expand a recent model of internal Ca2+ oscillations based on activation and inhibition of the IP3-receptor in the endoplasmic reticulum by introducing plasma membrane voltage-gated Ca2+ and K+ channels based on patch-clamp experiments on mouse pancreatic beta cells. Simulations of voltage- and current-clamped experiments are carried out. The amplitude and frequency of the oscillations as well as the sensitivity to agonist are strongly affected by altering the value of the voltage-clamp. We show that the fundamental quantity governing voltage clamp measurements is the inward flux of Ca2+, which acts as a control parameter to alter characteristics of the oscillations. Under current clamp conditions (I(applied) = 0) that lead to continuous spiking electrical activity, we examine the coupling between electrical activity and Ca2+ by introducing a small whole cell Ca(2+)-activated K+ conductance. Results of calculations are similar to those observed in agonist-stimulated beta cells and gonadotrophs. We conclude, however, that glucose-induced bursting and agonist induced bursting in beta cells are distinct phenomena and suggest a mechanism by which agonist-induced Ca2+ oscillations might potentiate insulin secretion. This leads to a general principle for selective signal transduction by Ca2+ oscillations.
Institute of Theoretical Dynamics, University of California, Davis.
J
J
Keizer
G
G
De Young
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008954:Models, Biological; D011188:Potassium / Q000494:pharmacology; D015398:Signal Transduction
D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate; D005947:Glucose; D011188:Potassium; D002118:Calcium