Calcium action potentials and potassium permeability activation in pancreatic beta-cells.

Ionic control mechanisms of mouse pancreatic beta-cell action potentials ("spikes"), in response to glucose, were studied by measuring membrane potentials with intracellular microelectrodes. The curve relating the peaks of the spikes to the log of the external calcium concentration above 10 mM has a slope of 25 mV/10-fold increase of Ca2+. This approaches the value predicted by the Nernst equation for a pure Ca2+ electrode. Increasing the external [Ca2+]o from 0 to 42.5 mM caused an increase in rates of spike depolarization and repolarization. Lowering [Ca2+]o or applying Ca2+ conductance blockers, including Co2+ (1.25 mM), Mn2+ (2mM), and D-600 (2 X 10(-4) M), caused a decrease in rates of spikes depolarization and repolarization, with an increase of [Ca2+]o reversing this effect. Higher concentrations of these Ca2+-conductance blockers eliminated the spike activity. Quinidine at a high concentration (10(-3) M) blocked spike repolarization. Tetraethylammonium (TEA, 25 mM) increased spike amplitude and duration. Therefore, it is concluded that Ca2+ entry during the spike affects potassium permeability, which is inhibited by TEA. Also, there is a competitive binding between Co2+, Mn2+, Mg2+, and Ca2+, the charge carrier. These cations may have an additional action of substituting for Ca2+ to "stabilize" the membrane.