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Histamine H 1 receptor activation blocks two classes of potassium current, I K(rest) and I AHP to excite ferret vagal afferents
Author(s) -
Jafri M. Samir,
Moore Kimberly A.,
Taylor Glen E.,
Weinreich Daniel
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.533bg.x
Subject(s) - histamine , chemistry , reversal potential , nodose ganglion , biophysics , hyperpolarization (physics) , membrane potential , apamin , histamine h1 receptor , pyrilamine , histamine h3 receptor , medicine , patch clamp , endocrinology , agonist , potassium channel , biology , receptor , vagus nerve , stereochemistry , biochemistry , stimulation , antagonist , nuclear magnetic resonance spectroscopy
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 μ m ) 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 ∼80% of the neurones. 3 Histamine (10 μ m ) also blocked the post‐spike slow after‐hyperpolarization (AHP slow ) present in 80% of these neurones (95 ± 3.2%; n = 5 ). All neurones possessing AHP slow in ferret nodose were C fibre neurones; all AHP slow neurones had conduction velocities ≤ 1 m s −1 ( n = 7 ). 4 Both the histamine‐induced inward current and the block of AHP slow were concentration dependent and each had an estimated EC 50 value of 2 μ m . These histamine‐induced effects were mimicked by the histamine H 1 receptor agonist 2‐(2‐aminoethyl)thiazole dihydrochloride (10 μ m ) and blocked by the H 1 antagonists pyrilamine (100 n m ) or diphenhydramine (100 n m ). Schild plot analysis of the effect of pyrilamine on the histamine‐induced inward current revealed a pA 2 value of 9.7, consistent with that expected for an H 1 receptor. Neither impromidine (10 μ m ) nor R (−)‐α‐methylhistamine (10 μ m ), selective H 2 or H 3 agonists, respectively, significantly affected the membrane potential, input resistance or AHP slow . 5 The reversal potential ( V rev ) for the histamine‐induced inward current was −84 ± 2.1 mV ( n = 4 ). The V rev 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 V rev of the histamine response ( n = 3 ). The V rev for the AHP slow 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 ( I K(rest )) and the potassium current underlying a post‐spike slow after‐hyper‐polarization ( I AHP ). Both these effects can occur in the same neurone and involve activation of the same histamine receptor subtype, the histamine H 1 receptor.