Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats

Abstract

Anti-histaminergic drugs have been widely used in the clinical treatment of vestibular disorders and most studies concentrate on their presynaptic actions. The present study investigated the postsynaptic effect of histamine on medial vestibular nucleus (MVN) neurons and the underlying mechanisms. Histamine-induced postsynaptic actions on MVN neurons and the corresponding receptor and ionic mechanisms were detected by whole-cell patch-clamp recordings on rat brain slices. The distribution of postsynaptic histamine H₁, H₂ and H₄ receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H₁, H₂ and H₄ receptors and for subtypes of Na⁺ -Ca²⁺ exchangers (NCXs) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels was assessed by quantitative real-time RT-PCR. A marked postsynaptic excitatory effect, co-mediated by histamine H₁ and H₂ receptors, was involved in the histamine-induced depolarization of MVN neurons. Postsynaptic H₁ and H₂ rather than H₄ receptors were co-localized in the same MVN neurons. NCXs contributed to the inward current mediated by H₁ receptors, whereas HCN channels were responsible for excitation induced by activation of H₂ receptors. Moreover, NCX1 and NCX3 rather than NCX2, and HCN1 rather than HCN2-4 mRNAs, were abundantly expressed in MVN. NCXs coupled to H₁ receptors and HCN channels linked to H₂ receptors co-mediate the strong postsynaptic excitatory action of histamine on MVN neurons. These results highlight an active role of postsynaptic mechanisms in the modulation by central histaminergic systems of vestibular functions and suggest potential targets for clinical treatment of vestibular disorders.