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

In glucose-stimulated pancreatic beta-cells, the membrane potential al ternates between a hyperpolarized silent phase and a depolarized phase with Ca2+ action potentials. The molecular and ionic mechanisms under lying these bursts of electric-al activity remain unknown. We have obs erved that 10.2-12.8 mM Ca2+, 1 muM Bay K 8644 and 2 mM tetraethylammo nium (TEA) trigger bursts of electrical activity and oscillations of i ntracellular free Ca2+ concentration ([Ca2+]i) in the presence of 100 muM tolbutamide. The [Ca2+]i was monitored from single islets of Lange rhans using fura-2 microfluorescence techniques. Both the high-Ca2+- a nd Bay-K-8644-evoked [Ca2+]i oscillations overshot the [Ca2+]i recorde d in tolbutamide. Nifedipine (10-20 muM) caused an immediate membrane hyperpolarization, which was followed by a slow depolarization to a le vel close to the burst active phase potential. The latter depolarizati on was accompanied by suppression of spiking activity. Exposure to hig h Ca2+ in the presence of nifedipine caused a steady depolarization of approximately 8 mV. Ionomycin (10 muM) caused membrane hyperpolarizat ion in the presence of 7.7 mM Ca2+, which was not abolished by nifedip ine. Charybdotoxin (CTX, 40-80 nM), TEA (2 mM) and quinine (200 muM) d id not suppress the high-Ca2+-evoked bursts. It is concluded that: (1) the channel underlying the burst is sensitive to [Ca2+]i rises mediat ed by Ca2+ influx through L-type Ca2+ channels, (2) both the ATP-depen dent K+ channel and the CTX- and TEA-sensitive Ca2+-dependent K+ chann el are highly unlikely to provide the pacemaker current underlying the burst. We propose that the burst is mediated by a distinct Ca2+-depen dent K+ channel and/or by [Ca2+]i-dependent slow processes of inactiva tion of Ca2+ currents.