title: Effects of octane derivatives on activity of the volume-regulated anion channel in rat pancreatic β-cells.
abstract: BACKGROUND
  Saturated free fatty acids (FFAs) have a dual action on pancreatic β-cells, consisting of an initial enhancement and subsequent suppression of glucose-induced electrical activity and insulin release. These stimulatory and inhibitory effects have been attributed, at least in part, to the activation and inhibition, respectively, of the volume-regulated anion channel (VRAC) by FFAs. Both effects were independent of their metabolism. We have now investigated the effects of related aliphatic compounds in order to further define the determinants of FFA interaction with VRAC.
  
  
  METHODS
  β-Cell VRAC and electrical activity were measured by conventional whole-cell and perforated patch recording, respectively. Cell volume was measured using a video-imaging technique.
  
  
  RESULTS
  In common with octanoic acid, addition of methyl octanoate or n-octanol resulted in a rapid, pronounced and reversible inhibition of VRAC activity. Addition of n-octane had no significant effect on VRAC activity. n-Octanol had a biphasic effect on β-cell membrane potential, namely a small transient depolarization followed by a marked hyperpolarization. n-Octanol was also found to prevent regulatory volume decrease in cells exposed to a hypotonic medium, consistent with VRAC inhibition.
  
  
  CONCLUSIONS
  It is suggested that methyl octanoate and n-octanol can mimic the effects of FFAs on the pancreatic β-cell via modulation of VRAC activity. The structural requirements for this effect appear to be a medium or long chain aliphatic compound containing at least one oxygen atom.
authors.affiliation: Faculties of Medical Sciences, University of Manchester, Oxford Road, Manchester, M13 9WL, UK. Leonard.Best2@ntlworld.com.
authors.forename: Len
authors.initials: L
authors.lastname: Best
authors.forename: Peter D
authors.initials: PD
authors.lastname: Brown
mesh_terms: D020003:1-Octanol / Q000494:pharmacology; D000818:Animals; D000838:Anions; D002210:Caprylates / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008564:Membrane Potentials; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D015394:Molecular Structure; D009795:Octanes / Q000737:chemistry / Q000494:pharmacology*; D009995:Osmosis; D051381:Rats; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000838:Anions; D002210:Caprylates; D007473:Ion Channels; D049990:Membrane Transport Modulators; D009795:Octanes; C039151:methyl octanoate; D020003:1-Octanol