Plateau potentials in pancreatic islet cells are voltage-dependent action potentials

Abstract

Islet cells stimulated by a steady glucose concentration above a certain threshold (usually 5–7 mM) display cyclic membrane potential changes¹. This islet electrical activity consists of action potentials (spikes) superimposed on a depolarized plateau (see Fig. 1). Higher levels of glucose prolong the plateau phase and shorten the silent phase until the plateau potentials merge to produce continuous spiking at 20–25 mM. The fraction of each cycle spent in the plateau phase correlates with glucose concentration and insulin release rate², suggesting that control of the onset and offset of the plateau is important in the regulation of insulin release. The abrupt transitions between silent and plateau phases suggest that the plateau is a persistent, voltage-dependent action potential as in cardiac muscle. This idea is supported by evidence³ that Ca²⁺ influx is stimulated by K⁺ depolarization of islets. However, this voltage dependency can be explained by electrical evidence^4,5 that the spikes are generated by voltage-dependent Ca²⁺ currents. Furthermore, there is evidence against the voltage dependency of the plateau because it seemed to be unaffected by intracellular current injection and K⁺ depolarization, which clearly affected spiking^5,6. As there are alternative explanations (see below) for these last negative findings, we have re-examined this important question using a new technique of direct electrical stimulation of entire, isolated islets using a suction electrode. Contrary to the previous negative findings, our present results clearly show that the plateau potential is a voltage-dependent, persistent action potential.