Neural Subtype-dependent Cholinergic Modulation of Neural Activities by Activation of Muscarinic 2 Receptors and G Protein-activated Inwardly Rectifying Potassium Channel in Rat Periaqueductal Gray Neurons.
Neuroscience
; 506: 1-13, 2022 12 01.
Article
em En
| MEDLINE
| ID: mdl-36270414
ABSTRACT
Acetylcholine plays a pivotal role in the regulation of functions such as pain and the sleep and wake cycle by modulating neural activities of the ventrolateral periaqueductal gray (vlPAG). Electrophysiological studies have shown that cholinergic effects are inconsistent among recorded neurons, particularly in the depolarization and hyperpolarization of the resting membrane potential (RMP). This discrepancy may be due to the neural subtype-dependent cholinergic modulation of the RMP. To examine this possibility, we performed whole-cell patch-clamp recordings from subtype-identified neurons using vesicular GABA transporter (VGAT)-Venus × ChAT-TdTomato rats and elucidated cellular mechanisms of cholinergic effects on the RMP. The application of carbachol hyperpolarized the RMP of cholinergic neurons in a dose-dependent manner but had much less of an effect on other neural subtypes, including GABAergic/glycinergic and glutamatergic neurons. Cholinergic hyperpolarization was accompanied by a decrease in input resistance. These cholinergic effects were blocked by AF-DX384 or gallamine and were mimicked by arecaidine but-2-ynyl ester tosylate, suggesting that the carbachol-induced hyperpolarization of the RMP in cholinergic neurons is mediated via M2 receptors. Tertiapin suppressed the carbachol-induced G protein-activated inwardly rectifying potassium channel (GIRK) currents and hyperpolarization of the RMP in cholinergic neurons. Intracellular application of GDP-ß-S blocked the carbachol-induced hyperpolarization of the RMP. Neostigmine slowly hyperpolarized the RMP in cholinergic neurons. These results suggest that neural firing of vlPAG cholinergic neurons is suppressed by GIRK currents induced via M2 receptor activation, and this negative feedback regulation of cholinergic neuronal activities can be induced by acetylcholine, which is intrinsically released in the vlPAG.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetilcolina
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Canais de Potássio Corretores do Fluxo de Internalização
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Receptor Muscarínico M2
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Neuroscience
Ano de publicação:
2022
Tipo de documento:
Article