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Muscarinic receptor modulation of GABA‐mediated giant depolarizing potentials in the neonatal rat hippocampus
Author(s) -
Avig Elena,
Cherubini Enrico
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.1469-7793.1999.0097r.x
Subject(s) - pirenzepine , carbachol , methoctramine , muscarinic acetylcholine receptor , endocrinology , medicine , chemistry , muscarinic acetylcholine receptor m1 , muscarinic acetylcholine receptor m2 , depolarization , acetylcholine , muscarinic acetylcholine receptor m3 , neuroscience , stimulation , biology , receptor
1 The whole‐cell patch clamp technique was used to study the role of muscarinic receptors in regulating the frequency of giant depolarizing potentials (GDPs) in CA3 hippocampal neurones in slices from postnatal (P) P1‐P8 rats. 2 Atropine (1 μM) reduced the frequency of GDPs by 64·2 ± 2·9 %. The acetylcholinesterase inhibitor edrophonium (20 μM) increased the frequency of GDPs in a developmentally regulated way. This effect was antagonized by the M1 muscarinic receptor antagonist pirenzepine. 3 In the presence of edrophonium, tetanic stimulation of cholinergic fibres induced either an enhancement of GDP frequency (179 ± 79 %) or a membrane depolarization (27 ± 16 mV) associated with an increase in synaptic noise. These effects were prevented by atropine. 4 Application of carbachol (3 μM) produced an increase in GDP frequency that at P5‐P6 was associated with a membrane depolarization and an increase in synaptic noise. These effects were prevented by atropine, pirenzepine (3 μM) and bicuculline (10 μM). 5 In the presence of pirenzepine, carbachol reduced GDP frequency by 50 ± 4 %. Conversely, in the presence of methoctramine (3 μM), carbachol enhanced GDP frequency by 117 ± 4 %. 6 It is concluded that endogenous acetylcholine, through the activation of M1 receptors, enhances the release of γ‐aminobutyric acid (GABA), in a developmentally regulated way. On the other hand, carbachol exerts both an up‐ and downregulation of GABA release through the activation of M1 and M2 receptors, respectively.