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Histamine Excites Neonatal Rat Sympathetic Preganglionic Neurons In Vitro Via Activation of H₁ Receptors

¹Warwick Medical School, University of Warwick, Coventry, United Kingdom; ²Neurosciences, Ottawa Health Research Institute, Ottawa, Ontario, Canada

Submitted 3 November 2004; accepted in final form 9 December 2005

The role of histamine in regulating excitability of sympathetic preganglionic neurons (SPNs) and the expression of histamine receptor mRNA in SPNs was investigated using whole-cell patch-clamp electrophysiological recording techniques combined with single-cell reverse transcriptase polymerase chain reaction (RT-PCR) in transverse neonatal rat spinal cord slices. Bath application of histamine (100 µM) or the H₁ receptor agonist histamine trifluoromethyl toluidide dimaleate (HTMT; 10 µM) induced membrane depolarization associated with a decrease in membrane conductance in the majority (70%) of SPNs tested, via activation of postsynaptic H₁ receptors negatively coupled to one or more unidentified K⁺ conductances. Histamine and HTMT application also induced or increased the amplitude and/or frequency of membrane potential oscillations in electrotonically coupled SPNs. The H₂ receptor agonist dimaprit (10 µM) or the H₃ receptor agonist imetit (100 nM) were without significant effect on the membrane properties of SPNs. Histamine responses were sensitive to the H₁ receptor antagonist triprolidine (10 µM) and the nonselective potassium channel blocker barium (1 mM) but were unaffected by the H₂ receptor antagonist tiotidine (10 µM) and the H₃ receptor antagonist, clobenpropit (5 µM). Single cell RT-PCR revealed mRNA expression for H₁ receptors in 75% of SPNs tested, with no expression of mRNA for H₂, H₃, or H₄ receptors. These data represent the first demonstration of H₁ receptor expression in SPNs and suggest that histamine acts to regulate excitability of these neurons via a direct postsynaptic effect on H₁ receptors.

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