BURSTING ELECTRICAL-ACTIVITY IN PANCREATIC BETA-CELLS - EVIDENCE THAT THE CHANNEL UNDERLYING THE BURST IS SENSITIVE TO CA2+ INFLUX THROUGH L-TYPE CA2+ CHANNELS

In glucose-stimulated pancreatic beta-cells, the membrane potential alternates between a hyperpolarized silent phase and a depolarized phase with Ca2+ action potentials. The molecular and ionic mechanisms underlying these bursts of electric-al activity remain unknown. We have observed that 10.2-12.8 mM Ca2+, 1 muM Bay K 8644 and 2 mM tetraethylammonium (TEA) trigger bursts of electrical activity and oscillations of intracellular free Ca2+ concentration ([Ca2+]i) in the presence of 100 muM tolbutamide. The [Ca2+]i was monitored from single islets of Langerhans using fura-2 microfluorescence techniques. Both the high-Ca2+- and Bay-K-8644-evoked [Ca2+]i oscillations overshot the [Ca2+]i recorded in tolbutamide. Nifedipine (10-20 muM) caused an immediate membrane hyperpolarization, which was followed by a slow depolarization to a level close to the burst active phase potential. The latter depolarization was accompanied by suppression of spiking activity. Exposure to high Ca2+ in the presence of nifedipine caused a steady depolarization of approximately 8 mV. Ionomycin (10 muM) caused membrane hyperpolarization in the presence of 7.7 mM Ca2+, which was not abolished by nifedipine. Charybdotoxin (CTX, 40-80 nM), TEA (2 mM) and quinine (200 muM) did not suppress the high-Ca2+-evoked bursts. It is concluded that: (1) the channel underlying the burst is sensitive to [Ca2+]i rises mediated by Ca2+ influx through L-type Ca2+ channels, (2) both the ATP-dependent K+ channel and the CTX- and TEA-sensitive Ca2+-dependent K+ channel are highly unlikely to provide the pacemaker current underlying the burst. We propose that the burst is mediated by a distinct Ca2+-dependent K+ channel and/or by [Ca2+]i-dependent slow processes of inactivation of Ca2+ currents.