Slow cholinergic excitation of guinea pig hippocampal neurons is mediated by two muscarinic receptor subtypes.

Stimulation of cholinergic fibers or bath application of carbachol (0.1-10 microM) induced a slow excitability increase in CA3 neurons and dentate granule cells of hippocampal slices. This effect which was antagonized by atropine (1 microM) was mediated by two receptor subtypes: a pirenzepine (10 microM)-insensitive receptor, 'M2', and a pirenzepine (1 microM)-sensitive receptor, 'M1'. The M2-receptor activation led to a blockade of slow afterhyperpolarizations following trains of action potentials and to the occurrence of threshold-activated plateau-depolarizations associated with a conductance increase. The M1-receptor mediated a membrane depolarization sometimes associated with a conductance decrease which reversed its polarity at membrane potentials negative to -80 mV. The 'slow excitatory postsynaptic potential' which results from activation of cholinergic fibers is thus caused by the activation of two receptor subtypes.