title: A new class of calcium channels activated by glucose in human pancreatic beta-cells.
abstract: Single calcium-channel currents were recorded from membrane patches of cultured beta-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 mV 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 mV 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 (greater than or equal to 11 mM), bursts of action potentials were often observed which were elicited only if Ca2+ was present in the solution bathing the beta-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-keto-isocaproate (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 beta-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.
authors.affiliation: Laboratory of Cell Biology and Genetics, NIDDK, National Institute of Health, Bethesda, MD 20892.
authors.forename: E
authors.initials: E
authors.lastname: Rojas
authors.forename: J
authors.initials: J
authors.lastname: Hidalgo
authors.forename: P B
authors.initials: PB
authors.lastname: Carroll
authors.forename: M X
authors.initials: MX
authors.lastname: Li
authors.forename: I
authors.initials: I
authors.lastname: Atwater
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000332:Aerobiosis; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002413:Cations, Divalent; D004553:Electric Conductivity; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000502:physiology*; D007651:Keto Acids / Q000494:pharmacology; D008356:Mannoheptulose / Q000494:pharmacology; D008564:Membrane Potentials; D013324:Strontium / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D002413:Cations, Divalent; D007651:Keto Acids; D001464:Barium; D008356:Mannoheptulose; C013082:alpha-ketoisocaproic acid; D005947:Glucose; D002118:Calcium; D013324:Strontium