Muscarinic M3 receptors inhibit a leak conductance in rat corticocallosal neurons.

Acetylcholine, acting on muscarinic receptors, has a powerful modulatory effect on neurons in the cerebral cortex. Recent evidence that cortical tissue contains at least four different muscarinic receptor subtypes having different pharmacological properties indicates the value of new investigations of the receptor subtypes that mediate electrophysiological responses. Here we studied the ionic nature and pharmacology of the depolarizing response to acetylcholine in identified corticocallosal neurons in primary culture. This response is the result of a non-rectifying 'leak' K+ conductance which is reduced in the presence of acetylcholine. The relative sensitivity of this conductance change to the antagonists pirenzepine and 4-DAMP suggests that it is mediated by the M3 subtype of muscarinic receptor.