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.
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