Effect of compartmentalized Ca2+ ions on electrical bursting activity of pancreatic beta-cells.
Patch-clamp single-channel and whole cell recordings have revealed new insights into the ionic channel properties in the pancreatic beta-cells. I have modeled the electrical events during the burst activity based on the observations that 1) the whole cell Ca2+ current has two functionally distinct components (fast and slow), 2) a fast component is inhibited by intracellular Ca2+, 3) a slow component is inactivated by depolarization, and 4) a significant fraction of the outward current is carried by the Ca2(+)-sensitive, voltage-gated K+ channels [K(Ca, V) channels]. The model contains a feature that the Ca2+ concentration in the submembrane compartment ([Ca2+]s) is higher than that in the cellular phase. At the plateau phase, [Ca2+]s is high enough to activate the K(Ca, V) channels. In addition to the K(Ca, V) channels, the model contains a voltage-activated Ca2+ channel that is quickly blocked by Ca2+ and slowly inhibited by voltage. Because the Ca2+ channel has an intracellular Ca2(+)-dependent inactivation gate, the increase in [Ca2+]s can inactivate the Ca2+ channels. According to this model, the spikes during the plateau phase are caused by a rapid movement of Ca2+ into and out of the compartment. Because of a rapid change in [Ca2+]s, the two competing currents, ICa and IK(Ca, V), fluctuate rapidly; the fluctuation leads to an emergence of spikes. The slow underlying wave is due to a voltage-dependent inactivation gate of the Ca2+ channels, which slowly closes as a result of depolarization. This model differs radically from my previous models, which featured a slowly varying intracellular Ca2+ concentration that was responsible for the underlying slow wave. Although the previous models give plateau fractions (the ratio between the plateau duration and cyclic time) to be far less than unity, the present model is the first of its kind that allows plateau fractions to be in the near-unity range.
Chay
T R
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Department of Biological Sciences, University of Pittsburgh, Pennsylvania 15260.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology*; D007700:Kinetics; D008433:Mathematics; D008564:Membrane Potentials; D008954:Models, Biological; D015221:Potassium Channels / Q000502:physiology
D015220:Calcium Channels; D015221:Potassium Channels; D002118:Calcium