Desensitization nicotinic acetylcholine receptors

Anatoxin-a is the most potent and most stereospecific nicotinic acetylcholine receptor agonist thus far identified. It is also highly selective for nicotinic receptors over muscarinic receptors. The molecular parameters which influence the binding affinity, channel activation, channel blockade, and receptor desensitization are being studied. Modifications of the carbonyl and amine moieties can reduce or nearly eliminate the receptor agonist potency of the compounds and also determine the channel blocking characteristics. 

Another complication is receptor desensitization. Desensitization of the nicotinic acetylcholine receptor is attributed to the receptor, especially in its activated form, changing spontaneously to a desensitized, inactive state. The following is a scheme incorporating all possible desensitized states of the receptor ... 

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Figure 9.7. Desensitization of the nicotinic acetylcholine receptor. a Experimental setup. Presynaptic action potentials were triggered, and postsynaptic ones were detected using two separate sets of electrodes, b Perfusion of the synapse with extraneous acetylcholine (during the time interval indicated by the horizontal brace) brings about a sudden depolarization. Continuous presence of acetylcholine rapidly suppresses the response to presynaptic action potentials also, the membrane potential returns to levels near the resting potential. Discontinuation of the acetylcholine results in restoration of response to presynaptic stimuli.

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These act as agonists at NM receptors. They induce initial fasciculation, then paralysis, through desensitization of nicotinic acetylcholine receptors (Nn). Succinylcholine is a drug in this class. 

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