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Muscarinic acetylcholine response in pyramidal neurones of rat cerebral cortex
Author(s) -
Nishikawa M.,
Munakata M.,
Akaike N.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13205.x
Subject(s) - oxotremorine , pirenzepine , muscarine , acetylcholine , muscarinic acetylcholine receptor , chemistry , endocrinology , medicine , inhibitory postsynaptic potential , reversal potential , muscarinic agonist , carbachol , atropine , biophysics , biology , patch clamp , biochemistry , receptor
1 The effects of acetylcholine (ACh) on pyramidal neurones acutely dissociated from the rat cerebral cortex were studied in the whole‐cell mode, by use of the nystatin‐perforated patch recording configuration. 2 ACh induced a net inward current ( I ACh ) accompanied by a membrane conductance decrease at a holding potential (V H ) of − 40 mV. I ACh increased in a concentration‐dependent manner with a half‐maximum concentration (EC 50 ) of 8.7 × 10 −7 M. 3 I ACh mainly resulted from the suppression of the voltage‐ and time‐dependent K + current (M‐current). 4 Muscarine and muscarinic agonists such as McN‐A‐343, oxotremorine and oxotremorine‐M mimicked the ACh response. The potency was in the order of oxotremorine‐M > McN‐A‐343 ≥ muscarine > oxotremorine. 5 Pirenzepine shifted the concentration‐response curve for ACh to the right and the corresponding Schild plot yielded a pA 2 value of 7.81. Other muscarinic antagonists also reversibly blocked I ACh in a concentration‐dependent manner. The inhibitory potency was in the order of atropine > 4‐DAMP > pirenzepine > AF‐DX‐116. 6 I ACh could be induced normally even after pre‐incubation of dissociated neurones in external solution with 200 ng ml −1 pertussis toxin (PTX) for 8 h, whereas the inhibitory effect of ACh on high‐voltage‐activated Ca 2+ channels was completely abolished by the PTX treatment.