title: A single polycystic kidney disease 2-like 1 channel opening acts as a spike generator in cerebrospinal fluid-contacting neurons of adult mouse brainstem.
abstract: Cerebrospinal fluid contacting neurons (CSF-cNs) are found around the central canal of all vertebrates. They present a typical morphology, with a single dendrite that projects into the cavity and ends in the CSF with a protuberance. These anatomical features have led to the suggestion that CSF-cNs might have sensory functions, either by sensing CSF movement or composition, but the physiological mechanisms for any such role are unknown. This hypothesis was recently supported by the demonstration that in several vertebrate species medullo-spinal CSF-cNs selectively express Polycystic Kidney Disease 2-Like 1 proteins (PKD2L1). PKD2L1 are members of the 'transient receptor potential (TRP)' superfamily, form non-selective cationic channels of high conductance, are regulated by various stimuli including protons and are therefore suggested to act as sensory receptors. Using patch-clamp whole-cell recordings of CSF-cNs in brainstem slices obtained from wild type and mutant PKD2L1 mice, we demonstrate that spontaneously active unitary currents in CSF-cNs are due to PKD2L1 channels that are capable, with a single opening, of triggering action potentials. Thus PKD2L1 might contribute to the setting of CSF-cN spiking activity. We also reveal that CSF-cNs have the capacity of discriminating between alkalinization and acidification following activation of specific conductances (PKD2L1 vs. ASIC) generating specific responses. Altogether, this study reinforces the idea that CSF-cNs represent sensory neurons intrinsic to the central nervous system and suggests a role for PKD2L1 channels as spike generators.
authors.affiliation: Aix Marseille Université, PPSN EA 4674, 13397, Marseille, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Orts-Del'Immagine
authors.affiliation: Aix Marseille Université, PPSN EA 4674, 13397, Marseille, France.
authors.forename: Riad
authors.initials: R
authors.lastname: Seddik
authors.affiliation: Aix Marseille Université, CNRS, CRN2M UMR 7286, 13344, Marseille, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Tell
authors.affiliation: Aix Marseille Université, PPSN EA 4674, 13397, Marseille, France.
authors.forename: Coraline
authors.initials: C
authors.lastname: Airault
authors.affiliation: Aix Marseille Université, PPSN EA 4674, 13397, Marseille, France; Université Sultan Moulay Slimane, 23000, Béni Mellal, Morocco.
authors.forename: Ghizlane
authors.initials: G
authors.lastname: Er-Raoui
authors.affiliation: Université Sultan Moulay Slimane, 23000, Béni Mellal, Morocco.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Najimi
authors.affiliation: Aix Marseille Université, PPSN EA 4674, 13397, Marseille, France. Electronic address: Jerome.trouslard@univ-amu.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Trouslard
authors.affiliation: Aix Marseille Université, PPSN EA 4674, 13397, Marseille, France. Electronic address: nicolas.wanaverbecq@univ-amu.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wanaverbecq
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001933:Brain Stem / Q000166:cytology*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000166:cytology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018684:Glycine Agents; C486487:Pkd2l1 protein, mouse; D011724:Pyridazines; D011956:Receptors, Cell Surface; D049452:Green Fluorescent Proteins; C049853:gabazine; D007736:Kynurenic Acid; D013331:Strychnine; D000109:Acetylcholine
keywords: 6,7-dinitroquinoxaline-2,3-dione disodium salt (DNQX) (PubChem CID: 45073428); AMPA; ASIC; Acetylcholine (PubChem CID: 187); Alkalinization; Brainstem; Cerebrospinal fluid contacting neurons; Gabazine (SR-95531) (PubChem CID: 107896); Gama-Amino butyric acid (GABA) (PubChem CID: 119); Glutamate (PubChem CID: 33032); Kainate; Kainate (PubChem CID: 22880); N-methyl-d-aspartic acid (NMDA) (PubChem CID: 22880); PKD2L1; Sensory; d-Tubocurarine (D-TC) (PubChem CID: 16000); dl-2-amino-5-phosphonopentanoic acid sodium salt (AP-V) (PubChem CID: 1216); nAChRs; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (PubChem CID: 158397)