title: VIP receptors control excitability of suprachiasmatic nuclei neurones.
abstract: The role of vasoactive intestinal polypeptide (VIP) receptors on excitable properties of neurones in slices acutely prepared from the suprachiasmatic nuclei (SCN) of wild-type (WT) and VPAC(2)-receptor-deficient (Vipr2 ( -/- )) mice was studied under voltage clamp with the use of patch-clamp recording in the whole-cell configuration. The resting membrane potential in Vipr2 ( -/- ) neurones was significantly hyperpolarised as compared to WT cells (-60+/-7 vs -72+/-6 mV, p<0.01). Bath application of 100 nM VIP or the VPAC(2) receptor agonist RO 25-1553 triggered a slow inward current in a subpopulation of WT SCN neurones; the VIP-induced current was not affected by slice incubation with 25 microM of bicuculline but disappeared completely when the cells were dialysed with CsCl-containing/K(+)-free solution. Application of VIP or RO 25-1553 to neurones from Vipr2 ( -/- ) mice did not induce currents in all cells tested. Incubation of WT slices with 100 nM VIP or RO 25-1553 resulted in inhibition of fast tetrodotoxin-sensitive sodium currents and delayed rectifier K(+) currents in most of the cells tested. This effect was completely absent in cells from Vipr2 ( -/- ) mice. We postulate that VIP receptors control excitability of SCN neurones at the postsynaptic level by direct modulation of membrane potential via inhibition of K(+) channels and by tonic inhibition of sodium and potassium voltage-gated currents.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, 1.124 Stopford Building, Oxford Road, M13 9PT, Manchester, UK.
authors.forename: Pavel
authors.initials: P
authors.lastname: Pakhotin
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Harmar
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
authors.forename: Hugh
authors.initials: H
authors.lastname: Piggins
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000502:physiology*
chemical_list: D015221:Potassium Channels; D018005:Receptors, Vasoactive Intestinal Peptide; D012964:Sodium; D011188:Potassium