Lack of dystrophin functionally affects alpha 3 beta 2/beta 4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice

In the sympathetic superior cervical ganglion (SCG), nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission. We previously demonstrated that in SCG neurons of mdx mice, an animal model for Duchenne muscular dystrophy, lack of dystrophin causes a decrease, compared to the wild-type, in postsynaptic nAChRs containing the alpha 3 subunit associated with beta 2 and/or beta 4 (alpha 3 beta 2/beta 4-nAChRs), but not in those containing the alpha 7 subunit. Here we show, by whole cell patch-clamp recordings from cultured SCG neurons, that both nicotine and acetylcholine-evoked currents through alpha 3 beta 2/beta 4-nAChRs are significantly reduced in mdx mice compared to the wild-type, while those through ea-nAChR are unaffected. This reduction associates with that of protein levels of alpha 3, beta 2 and beta 4 subunits. Therefore, we suggest that, in mdx mouse SCG neurons, lack of dystrophin, by specifically affecting membrane stabilization of alpha 3 beta 2/beta 4-nAChRs, could determine an increase in receptor internalization and degradation, with consequent reduction in the fast intraganglionic cholinergic transmission. (c) 2010 Elsevier Inc. All rights reserved