Lack of dystrophin functionally affects α3β2/β4-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 post-synaptic nAChRs containing the α3 subunit associated with β2 and/or β4 (α3β2/β4-nAChRs), but not in those containing the α7 subunit. Here we show, by whole cell patch-clamp recordings from cultured SCG neurons, that both nicotine and acetylcholine-evoked currents through α3β2/β4-nAChRs are significantly reduced in mdx mice compared to the wild-type, while those through α7-nAChR are unaffected. This reduction associates with that of protein levels of α3, β2 and β4 subunits. Therefore, we suggest that, in mdx mouse SCG neurons, lack of dystrophin, by specifically affecting membrane stabilization of α3β2/β4-nAChRs, could determine an increase in receptor internalization and degradation, with consequent reduction in the fast intraganglionic cholinergic transmission.
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie Charles Darwin, Sapienza Università di Roma, Italy.
Silvia
S
Di Angelantonio
Maria Egle
ME
De Stefano
Alessio
A
Piccioni
Loredana
L
Lombardi
Cecilia
C
Gotti
Paola
P
Paggi
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D055550:Protein Stability; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
D016189:Dystrophin; D011978:Receptors, Nicotinic