Background and purpose
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. Experimental approach: 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 H&sub1;, H&sub2; and H&sub4; receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H&sub1;, H&sub2; and H&sub4; 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. Key
Purpose
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. Experimental approach: 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 H&sub1;, H&sub2; and H&sub4; receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H&sub1;, H&sub2; and H&sub4; 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. Key
Results
A marked postsynaptic excitatory effect, co-mediated by histamine H&sub1; and H&sub2; receptors, was involved in the histamine-induced depolarization of MVN neurons. Postsynaptic H&sub1; and H&sub2; rather than H&sub4; receptors were co-localized in the same MVN neurons. NCXs contributed to the inward current mediated by H&sub1; receptors, whereas HCN channels were responsible for excitation induced by activation of H&sub2; receptors. Moreover, NCX1 and NCX3 rather than NCX2, and HCN1 rather than HCN2-4 mRNAs, were abundantly expressed in MVN.