VIP receptors control excitability of suprachiasmatic nuclei neurones

P Pakhotin, A J Harmar, A Verkhratsky, H Piggins

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 kipr2(-/-) neurones was significantly hyperpolarised as compared to WT cells (-60 +/- 7vs-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 mu M of bicuculline but disappeared completely when the cells were dialysed with CsClcontaining/K+-free solution. Application of VIP or RO 25-1553 to neurones from Fipr2(-/-) 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+ cur-rents in most of the cells tested. This effect was completely absent in cells from kipr2(-/-) 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.

Original languageEnglish
Pages (from-to)7-15
Number of pages9
JournalPflügers Archiv European Journal of Physiology
Volume452
Issue number1
DOIs
Publication statusPublished - Apr 2006

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