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On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus
Author(s) -
Brown Ritchie E.,
Haas Helmut L.
Publication year - 1999
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.1469-7793.1999.777ab.x
Subject(s) - thioperamide , histaminergic , histamine h3 receptor , chemistry , neurotransmission , histamine , histamine receptor , excitatory postsynaptic potential , dentate gyrus , pharmacology , endocrinology , medicine , biology , agonist , antagonist , biochemistry , receptor , hippocampus
1 Histaminergic depression of excitatory synaptic transmission in the rat dentate gyrus was investigated using extracellular and whole‐cell patch‐clamp recording techniques in vitro . 2 Application of histamine (10 μ m , 5 min) depressed synaptic transmission in the dentate gyrus for 1 h. This depression was blocked by the selective antagonist of histamine H 3 receptors, thioperamide (10 μ m ). 3 The magnitude of the depression caused by histamine was inversely related to the extracellular Ca 2+ concentration. Application of the N‐type calcium channel blocker ω‐conotoxin (0.5 or 1 μ m ) or the P/Q‐type calcium channel blocker ω‐agatoxin (800 n m ) did not prevent depression of synaptic transmission by histamine. 4 The potassium channel blocker 4‐aminopyridine (4‐AP, 100 μ m ) enhanced synaptic transmission and reduced the depressant effect of histamine (10 μ m ). 4‐AP reduced the effect of histamine more in 2 m m extracellular calcium than in 4 m m extracellular calcium. 5 Histamine (10 μ m ) did not affect the amplitude of miniature excitatory postsynaptic currents (mEPSCs) and had only a small effect on their frequency. 6 Histaminergic depression was not blocked by an inhibitor of serine/threonine protein kinases, H7 (100 μ m ), or by an inhibitor of tyrosine kinases, Lavendustin A (10 μ m ). 7 Application of adenosine (20 μ m ) or the adenosine A 1 agonist N 6 ‐cyclopentyladenosine (CPA, 0.3 μ m ) completely occluded the effect of histamine (10 μ m ). 8 We conclude that histamine, acting on histamine H 3 receptors, inhibits glutamate release by inhibiting presynaptic calcium entry, via a direct G‐protein‐mediated inhibition of multiple calcium channels. Histamine H 3 receptors and adenosine A 1 receptors act upon a common final effector to cause presynaptic inhibition.