title: Histamine H1 receptor activation blocks two classes of potassium current, IK(rest) and IAHP, to excite ferret vagal afferents.
abstract: 1. Intracellular recordings were made in intact and acutely dissociated vagal afferent neurones (nodose ganglion cells) of the ferret to investigate the membrane effects of histamine. 2. In current-clamp or voltage-clamp recordings, histamine (10 microM) depolarized the membrane potential (10 +/- 0.8 mV; mean +/- S.E.M.; n = 27) or produced an inward current of 1.6 +/- 0.35 nA (n = 27) in approximately 80% of the neurones. 3. Histamine (10 microM) also blocked the post-spike slow after-hyperpolarization (AHP slow) present in 80% of these neurones (95 +/- 3.2%; n = 5). All neurones possessing AHPslow in ferret nodose were C fibre neurones; all AHPslow neurones had conduction velocities < or = 1 m s-1 (n = 7). 4. Both the histamine-induced inward current and the block of AHPslow were concentration dependent and each had an estimated EC50 value of 2 microM. These histamine-induced effects were mimicked by the histamine H1 receptor agonist 2-(2-aminoethyl) thiazole dihydrochloride (10 microM) and blocked by the H1 antagonists pyrilamine (100 nM) or diphenhydramine (100 nM). Schild plot analysis of the effect of pyrilamine on the histamine-induced inward current revealed a pA2 value of 9.7, consistent with that expected for an H1 receptor. Neither impromidine (10 microM) nor R(-)-alpha-methylhistamine (10 microM), selective H2 or H3 agonists, respectively, significantly affected the membrane potential, input resistance or AHPslow. 5. The reversal potential (Vrev) for the histamine-induced inward current was -84 +/- 2.1 mV (n = 4). The Vrev for the histamine response shifted in a Nernstian manner with changes in the extracellular potassium concentration. Alterations in the extracellular chloride concentration had no significant effect on the Vrev of the histamine response (n = 3). The Vrev for the AHPslow was -85 +/- 1.7 mV (n = 4). 6. These results indicate that histamine increases the excitability of ferret vagal afferent somata by interfering with two classes of potassium current: the resting or 'leak' potassium current (IK(rest)) and the potassium current underlying a post-spike slow after-hyperpolarization (IAHP). Both these effects can occur in the same neurone and involve activation of the same histamine receptor subtype, the histamine H1 receptor.
authors.affiliation: University of Maryland, School of Medicine, Department of Pharmacology and Experimental Therapeutics, Baltimore 21201-1559, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Jafri
authors.forename: K A
authors.initials: KA
authors.lastname: Moore
authors.forename: G E
authors.initials: GE
authors.lastname: Taylor
authors.forename: D
authors.initials: D
authors.lastname: Weinreich
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004155:Diphenhydramine / Q000494:pharmacology; D004553:Electric Conductivity; D005289:Ferrets; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D017446:Impromidine / Q000494:pharmacology; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009475:Neurons, Afferent / Q000737:chemistry / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism* / Q000493:pharmacokinetics; D026902:Potassium Channel Blockers; D011738:Pyrilamine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*
chemical_list: D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D008761:Methylhistamines; D026902:Potassium Channel Blockers; D011969:Receptors, Histamine H1; D013844:Thiazoles; C029345:2-(2-aminoethyl)thiazole; C069357:alpha-methylhistamine; D006632:Histamine; D004155:Diphenhydramine; D017446:Impromidine; D011738:Pyrilamine; D011188:Potassium