Botulinum toxin converts muscle acetylcholine receptors from adult to embryonic type

To assess the postsynaptic consequences of botulinum toxin injection into muscle we characterized the nicotinic acetylcholine receptor (nAChR) with the patch clamp technique, using adult mouse muscle after destruction of the nerve ending and after treatment with botulinum toxin (BoTX). In both, embryonic channels with a conductance of 30 and 34 pS could be identified, whereas on adult control muscle nAChR channels had a conductance of 48 pS. The mean open times were 1.2 ms for the channels in control, 2.5 ms in denervated and 2.4 ms in BoTX-treated muscle. The dose-response curves of the maximal acetylcholine-elicited currents showed a Km of 60 mumol/L for denervated, 70 mumol/L for BoTX-treated, and 100 mumol/L for control muscle. Destruction of the nerve ending and inhibition of acetylcholine release by BoTX has the same effect as far as the increase of sensitivity of the muscle to acetylcholine is concerned. In contrast to single-fiber EMG findings in patients treated for focal dystonia no distant changes could be found in the control muscle of the BoTX-treated animals.