title: Muscarinic autoreceptors related with calcium channels in the strong and weak inputs at polyinnervated developing rat neuromuscular junctions.
abstract: Using intracellular recording, we studied how several muscarinic antagonists affected the evoked endplate potentials in singly and dually innervated endplates of the levator auris longus muscle from 3 to 6-day-old rats. In dually innervated fibers, a second endplate potential (EPP) may appear after the first one when we increase the stimulation intensity. The lowest and highest EPP amplitudes are designated "small-EPP" and "large-EPP," respectively. In singly innervated endplates and large-EPP, we found an inhibition of acetylcholine release by M1-receptor antagonists pirenzepine and MT-7 (more than 30%) and M2-receptor antagonists methoctramine and AF-DX 116 (more than 40%). The small-EPP was also inhibited by both M2-receptor antagonists methoctramine (approximately 70%) and AF-DX 116 (approximately 40%). However, the small-EPP was enhanced by M1-receptor antagonists pirenzepine (approximately 90%) and MT-7 (approximately 50%). The M4-receptor selective antagonists tropicamide and MT-3 can also increase the small-EPP amplitude (75% and 120%, respectively). We observed a graded change from a multichannel involvement (P/Q- N- and L-type voltage-dependent calcium channels) of all muscarinic responses (M1-, M2- and M4-mediated) in the small-EPP to the single channel (P/Q-type) involvement of the M1 and M2 responses in the singly innervated endplates. This indicates the existence of a progressive calcium channels shutoff in parallel with the specialization of the adult type P/Q channel. In conclusion, muscarinic autoreceptors can directly modulate large-EPP generating ending potentiation, and small-EPP generating ending depression through their association with the calcium channels during development.
authors.affiliation: Unitat d'Histologia i Neurobiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St. Llorenç num 21, 43201, Reus, Spain. msm@fmcs.urv.es
authors.forename: M M
authors.initials: MM
authors.lastname: Santafé
authors.forename: I
authors.initials: I
authors.lastname: Salon
authors.forename: N
authors.initials: N
authors.lastname: Garcia
authors.forename: M A
authors.initials: MA
authors.lastname: Lanuza
authors.forename: O D
authors.initials: OD
authors.lastname: Uchitel
authors.forename: J
authors.initials: J
authors.lastname: Tomàs
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017660:Autoreceptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D009045:Motor Endplate / Q000187:drug effects / Q000254:growth & development; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000254:growth & development*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*
chemical_list: D017660:Autoreceptors; D015220:Calcium Channels; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic