Cyclic changes in potential and resistance of the beta-cell membrane induced by glucose in islets of Langerhans from mouse

Abstract

1. The effects of KCl on the membrane potential were studied in cells from mouse islets of Langerhans identified as beta-cells by the characteristic pattern of electrical activity induced by 11.1 mM glucose. 2. In the absence of glucose, when the beta-cell membrane does not exhibit electrical activity, the dependence of the membrane potential upon external potassium [K+]o, could be described by the constant field equation using a PK/PNa ratio between 30 and 75. 3. In 11.1 mM glucose, when the beta-cell membrane potential fluctuates between a silent phase at about -50 mV and an active phase at about -40 mV giving rise to a train of spikes, the dependence of the membrane potential upon [K+]o could also be described with the constant field equation using a smaller PK/PNa of about 15, during the silent phase, and of about 8, during the active phase (foot of the spikes during the burst). 4. A bridge amplifier for measuring the changes in membrane potential during the application of pulses of current through the same micro-electrode was used to estimate the input resistance of a beta-cell. In 11.1 mM glucose, rough estimates of the membrane resistance during the silent phase averaged 1.2 X 10(8) omega. 5. The time course of the changes in input resistance of the cell when switching from 0 to 11.1 mM glucose showed a transient decrease from 0.9 X 10(8) to 0.7 X 10(8) omega followed by an increase to 1.2 X 10(8) omega. 6. The burst pattern was shown to result from the superposition of two potential changes: (a) 5--10 mV depolarization (lasting about 10 sec in 11.1 mM glucose), and (b) 10--50 mM spikes (lasting about 0.1 sec). Only the latter could be suppressed by hyperpolarizing current injection. 7. Application of pulses of current during the various phases of the electrical activity in 11.1 mM glucose enable us to compare the resistance during the silent and active phases. This was found to be oscillating between a high resistance value at about 1.2 X 10(8) omega before each burst and a low resistance value at 0.9 X 10(8) omega during the active phase at the foot of the spikes. In some cells the resistance during the silent phase remained fairly constant. In other cells it increased gradually from 1.1 X 10(8) to 1.3 X 10(8) omega measured just before each burst of spikes. 8. The observed increase in resistance induced by glucose together with the measured dependency of the membrane potential on [K+]o with and without glucose can be explained by postulating that in the presence of glucose the K+ permeability of the beta-cell membrane is reduced. 9. The oscillations between a high and a low resistance state in the presence of 11.1 mM glucose could be due to a sudden decrease in K+ permeability followed by a much larger increase in permeability to other ions, presumably Na+ and Ca2+.