Calcium-dependent pirenzepine-sensitive muscarinic response in the rat hippocampal slice.

Using intracellular recording techniques in the rat hippocampal slice, we observed that muscarinic agonists produce a transient Ca2+-dependent depolarization that may be related to the phosphatidylinositol cycle. First, it was more readily produced by muscarinic group A agonists, which strongly enhance the breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) than by group B agonists, which are less efficacious. Second, the Ca2+-dependent response was blocked by pirenzepine (PRZ), a selective muscarinic antagonist that blocks PIP2 breakdown in forebrain. Both group A and group B muscarinic agonists caused equivalent maintained levels of depolarization that were relatively insensitive to PRZ. The data suggest that the Ca2+-dependent response is fundamentally unlike other muscarinic responses that have been described in hippocampus.