VIP receptors control excitability of suprachiasmatic nuclei neurones

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.