A single polycystic kidney disease 2-like 1 channel opening acts as a spike generator in cerebrospinal fluid-contacting neurons of adult mouse brainstem

Neuropharmacology. 2016 Feb;101:549-65. doi: 10.1016/j.neuropharm.2015.07.030. Epub 2015 Jul 26.


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.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Brain Stem / cytology*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cerebrospinal Fluid / cytology*
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Glycine Agents / pharmacology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • In Vitro Techniques
  • Kynurenic Acid / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Pyridazines / pharmacology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Strychnine / pharmacology


  • Calcium Channels
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Glycine Agents
  • Pkd2l1 protein, mouse
  • Pyridazines
  • Receptors, Cell Surface
  • Green Fluorescent Proteins
  • gabazine
  • Kynurenic Acid
  • Strychnine
  • Acetylcholine