MUSCARINIC ACETYLCHOLINE RESPONSE IN PYRAMIDAL NEURONS OF RAT CEREBRAL-CORTEX

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 x 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 greater than or equal to 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>pir-enzepine> 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 Ca2+ channels was completely abolished by the PTX treatment.