A NEW CLASS OF CALCIUM CHANNELS ACTIVATED BY GLUCOSE IN HUMAN PANCREATIC BETA-CELLS

Single calcium-channel currents were recorded from membrane patches of cultured β-cells dissociated from human islets of Langerhans. In the absence of exogenous glucose, low frequency spontaneous calcium-channel openings of small amplitude (-0.34 ± 0.02 pA at 0 m V pipet potential) were observed in all membrane patches examined (25 mM Ca2+ in the patch pipet). The frequency of channel openings was rather insensitive to the membrane potential across the patch (range from ca 0 to 60 m V pipet potential; chord conductance 4.9 ± 0.2 pS). Addition of glucose induced a dose-dependent increase in the frequency of openings of the Ca2+-channel (from now on referred to as the CaG-channel). A few minutes after the addition of glucose (≥ 11 mM), bursts of action potentials were often observed which were elicited only if Ca2+ was present in the solution bathing the β-cells. Application of glucose in the presence of mannoheptulose (11 mM), a blocker of the hexokinase controlling the first stage of glycolysis, had no effect and the activity of the CaG-channel remained at its resting level. The readily permeant mitochondrial substrate 2-ketoisocaproate (KIC, 10 mM) was as effective as glucose in eliciting action potentials from cells forming part of cell aggregates. The activity of the CaG-channel was significantly increased by KIC (11 mM). Although spike and Ca2+-channel activity were markedly stimulated by glucose or KIC in all cells examined, regular bursts of action potentials were seen only if the patch was formed on β-cells which were part of a cell aggregate. Mannoheptulose (11 mM) prevented the activation of the CaG-channel by glucose (11 mM) but not by KIC (11 mM). Once activated, the CaG-channel remained active even after excision of the patch. We propose that the physiological control of this Ca2+-channel is mediated by one or more products of glucose metabolism. © 1990.