Studies of muscarinic neurotransmission with antimuscarinic toxins.

M1 and M4 muscarinic receptors are the most prevalent receptors for acetylcholine in the brain, and m1-toxin1 and m4-toxin are the most specific ligands yet found for their extracellular faces. Both toxins are antagonists. These toxins and their derivatives with biotin, radioiodine and fluorophores are useful for studying M1- and M4-linked neurotransmission. We have used the rat striatum for many studies because this tissue express exceptionally high concentrations of both receptors, the striatum regulates movement, and movement is altered by antimuscarinic agents, M1-knockout and M4-knockout. These toxins and their derivatives may also be used for studies of M1 and M4 receptors in the hippocampus and cortex.