MK-801 blocks nicotinic depolarizations of guinea pig myenteric neurons

Intracellular recordings were made from guinea-pig myenteric neurons. Acetylcholine (ACh), applied by iontophoresis, produced a depolarization that was blocked by hexamethonium (EC50 3.2 microM) but not by scopolamine (1 microM). MK-801 (0.3-30 microM), a non-competitive antagonist at N-methyl-D-aspartate receptors, also blocked the nicotinic depolarization (EC50 = 4.5 microM). Voltage clamp measurements of membrane current showed that MK-801 (1 microM) and hexamethonium (1 microM) both produced a greater inhibition of ACh-induced inward currents at -100 mV than at -40 mV. MK-801 (10 microM) did not change the depolarization evoked by 5-HT (acting at 5-HT3 receptors) in the same neurons in which it reduced the nicotinic response by more than 70%. It is concluded that MK-801 can act as a non-competitive antagonist of nicotinic responses in myenteric neurons.