title: Slow potentials encode intercellular coupling and insulin demand in pancreatic beta cells.
abstract: OBJECTIVE
  Ion fluxes constitute a major integrative signal in beta cells that leads to insulin secretion and regulation of gene expression. Understanding these electrical signals is important for deciphering the endogenous algorithms used by islets to attain homeostasis and for the design of new sensors for monitoring beta cell function.
  
  
  METHODS
  Mouse and human islets were cultured on multielectrode arrays (MEAs) for 3-13 days. Extracellular electrical activities received on each electrode were continuously amplified and recorded for offline characterisation.
  
  
  RESULTS
  Differential band-pass filtering of MEA recordings of mouse islets showed two extracellular voltage waveforms: action potentials (lasting 40-60 ms) and very robust slow potentials (SPs, lasting 800-1,500 ms), the latter of which have not been described previously. The frequency of SPs directly correlated with glucose concentration, peaked at 10 mmol/l glucose and was further augmented by picomolar concentrations of glucagon-like peptide-1. SPs required the closure of ATP-dependent potassium channels as they were induced by glucose or glibenclamide but were not elicited by KCl-induced depolarisation. Pharmacological tools and the use of beta cell specific knockout mice showed that SPs reflected cell coupling via connexin 36. Moreover, increasing and decreasing glucose ramps showed hysteresis with reduced glucose sensitivity during the decreasing phase. SPs were also observed in human islets and could be continuously recorded over 24 h.
  
  
  CONCLUSIONS
  This novel electrical signature reflects the syncytial function of the islets and is specific to beta cells. Moreover, the observed hysteresis provides evidence for an endogenous algorithm naturally present in islets to protect against hypoglycaemia.
authors: CNRS UMR 5248, Chimie et Biologie des Membranes et Nano-objets, Université de Bordeaux, Batiment B14, Allée Geoffroy St Hilaire, CS90063, 33615, Pessac, France.
authors: Fanny
authors: F
authors: Lebreton
authors: Antoine
authors: A
authors: Pirog
authors: Isma
authors: I
authors: Belouah
authors: Domenico
authors: D
authors: Bosco
authors: Thierry
authors: T
authors: Berney
authors: Paolo
authors: P
authors: Meda
authors: Yannick
authors: Y
authors: Bornat
authors: Bogdan
authors: B
authors: Catargi
authors: Sylvie
authors: S
authors: Renaud
authors: Matthieu
authors: M
authors: Raoux
authors: Jochen
authors: J
authors: Lang
mesh_terms: D000465:Algorithms; D000818:Animals; D002478:Cells, Cultured; D004566:Electrodes; D055724:Electrophysiological Phenomena; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology*; D007477:Ions; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012815:Signal Processing, Computer-Assisted; D015398:Signal Transduction
chemical_list: D007328:Insulin; D007477:Ions; D005947:Glucose