A quantitative pharmacological study of the cholinergic depolarization of hippocampal pyramidal cells in rat brain slices

Intracellular recordings were performed in rat brain slices and the pharmacology of the depolarizing effect of cholinomimetic drugs on hippocampus CA1 pyramidal cells was quantitatively investigated Acetylcholine (ACh) and muscarine induced a concentration-dependent depolarization of these cells. The EC50 values were respectively 159 +/- 54 mu M and 0.7 +/- 0.15 mu M. Physostignmine (1 mu M) or tacrine (1 mu M) induced a marked shift in the concentration-response curve for ACh. Both drugs were equipotent in this respect. The EC50 values for ACh became, respectively, 2.4 +/- 1.5 mu M and 3 +/- 0.9 mu M. The depolarizing effect of ACh was completely blocked by atropine, confirming the involvement of a receptor of the muscarinic type. In order to determine the subtype of muscarinic receptor involved, the EC50 values of muscarine were determined in the presence of atropine (100 nM), pirenzepine (1 mu M) or AFDX116 (10 mu M). The deduced pK(B) for the antagonists were, respectively, 8.9, 7.4 and 6.5. Comparison with binding data suggests that M-1 receptors play a prominent role in the depolarizing effect of cholinomimetic drugs on CA1 pyramidal cells.