title: Early development of electrical excitability in the mouse enteric nervous system.
abstract: Neural activity is integral to the development of the enteric nervous system (ENS). A subpopulation of neural crest-derived cells expresses pan-neuronal markers at early stages of ENS development (at E10.5 in the mouse). However, the electrical activity of these cells has not been previously characterized, and it is not known whether all cells expressing neuronal markers are capable of firing action potentials (APs). In this study, we examined the activity of "neuron"-like cells (expressing pan-neuronal markers or with neuronal morphology) in the gut of E11.5 and E12.5 mice using whole-cell patch-clamp electrophysiology and compared them to the activity of neonatal and adult enteric neurons. Around 30-40% of neuron-like cells at E11.5 and E12.5 fired APs, some of which were very similar to those of adult enteric neurons. All APs were sensitive to tetrodotoxin (TTX), indicating that they were driven by voltage-gated Na+ currents. Expression of mRNA encoding several voltage-gated Na+ channels by the E11.5 gut was detected using RT-PCR. The density of voltage-gated Na+ currents increased from E11.5 to neonates. Immature active responses, mediated in part by TTX- and lidocaine-insensitive channels, were observed in most cells at E11.5 and E12.5, but not in P0/P1 or adult neurons. However, some cells expressing neuronal markers at E11.5 or E12.5 did not exhibit an active response to depolarization. Spontaneous depolarizations resembling excitatory postsynaptic potentials were observed at E12.5. The ENS is one of the earliest parts of the developing nervous system to exhibit mature forms of electrical activity.
authors.affiliation: Department of Anatomy, University of Melbourne, and Florey Neuroscience Institutes, Melbourne, Victoria 3010, Australia.
authors.forename: Marlene M
authors.initials: MM
authors.lastname: Hao
authors.forename: Alan E
authors.initials: AE
authors.lastname: Lomax
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: McKeown
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Reid
authors.forename: Heather M
authors.initials: HM
authors.lastname: Young
authors.forename: Joel C
authors.initials: JC
authors.lastname: Bornstein
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000367:Age Factors; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D055592:Biophysical Phenomena / Q000502:physiology*; D001703:Biophysics; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D017615:Enteric Nervous System / Q000166:cytology / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins; D008012:Lidocaine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000378:metabolism; D018709:Statistics, Nonparametric; D013779:Tetrodotoxin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D000779:Anesthetics, Local; D015222:Sodium Channels; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D008012:Lidocaine; D014446:Tyrosine 3-Monooxygenase