Activation of Ca2+-dependent K+ channels contributes to rhythmic firing ofaction potentials in mouse pancreatic beta cells

We have applied the perforated patch whole-cell technique to beta cells wit hin intact pancreatic islets to identify the current underlying the glucose -induced rhythmic firing of action potentials. Trains of depolarizations (t o simulate glucose-induced electrical activity) resulted in the gradual (ti me constant: 2.3 s) development of a small (<0.8 nS) K+ conductance. The cu rrent was dependent on Ca2+ influx but unaffected by apamin and charybdotox in, two blockers of Ca2+-activated K+ channels, and was insensitive to tolb utamide (a blocker of ATP-regulated K+ channels) but partially (>60%) block ed by high (10-20 mM) concentrations of tetraethylammonium. Upon cessation of electrical stimulation, the current deactivated exponentially with a tim e constant of 6.5 s. This is similar to the interval between two successive bursts of action potentials. We propose that this Ca2+-activated K+ curren t plays an important role in the generation of oscillatory electrical activ ity in the beta cell.