title: Role of connexin 32 hemichannels in the release of ATP from peripheral nerves.
abstract: Extracellular purines elicit strong signals in the nervous system. Adenosine-5'-triphosphate (ATP) does not spontaneously cross the plasma membrane, and nervous cells secrete ATP by exocytosis or through plasma membrane proteins such as connexin hemichannels. Using a combination of imaging, luminescence and electrophysiological techniques, we explored the possibility that Connexin 32 (Cx32), expressed in Schwann cells (SCs) myelinating the peripheral nervous system could be an important source of ATP in peripheral nerves. We triggered the release of ATP in vivo from mice sciatic nerves by electrical stimulation and from cultured SCs by high extracellular potassium concentration-evoked depolarization. No ATP was detected in the extracellular media after treatment of the sciatic nerve with Octanol or Carbenoxolone, and ATP release was significantly inhibited after silencing Cx32 from SCs cultures. We investigated the permeability of Cx32 to ATP by expressing Cx32 hemichannels in Xenopus laevis oocytes. We found that ATP release is coupled to the inward tail current generated after the activation of Cx32 hemichannels by depolarization pulses, and it is sensitive to low extracellular calcium concentrations. Moreover, we found altered ATP release in mutated Cx32 hemichannels related to the X-linked form of Charcot-Marie-Tooth disease, suggesting that purinergic-mediated signaling in peripheral nerves could underlie the physiopathology of this neuropathy.
authors.affiliation: Department of Pathology and Experimental Therapeutics, Faculty of Medicine-Campus Bellvitge, University of Barcelona, Hospitalet del Llobregat, Barcelona, Spain; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Nualart-Marti
authors.forename: Ezequiel Mas
authors.initials: EM
authors.lastname: del Molino
authors.forename: Xènia
authors.initials: X
authors.lastname: Grandes
authors.forename: Laia
authors.initials: L
authors.lastname: Bahima
authors.forename: Mireia
authors.initials: M
authors.lastname: Martin-Satué
authors.forename: Rafel
authors.initials: R
authors.lastname: Puchal
authors.forename: Ilaria
authors.initials: I
authors.lastname: Fasciani
authors.forename: Daniel
authors.initials: D
authors.lastname: González-Nieto
authors.forename: Bulat
authors.initials: B
authors.lastname: Ziganshin
authors.forename: Artur
authors.initials: A
authors.lastname: Llobet
authors.forename: Luis C
authors.initials: LC
authors.lastname: Barrio
authors.forename: Carles
authors.initials: C
authors.lastname: Solsona
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D017629:Gap Junctions / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism*; D014982:Xenopus laevis; D000097002:Gap Junction beta-1 Protein
chemical_list: D000255:Adenosine Triphosphate; D002229:Carbenoxolone; D017630:Connexins; D000097002:Gap Junction beta-1 Protein
keywords: Schwann cell; X-linked Charcot-Marie-Tooth disease; Xenopus oocytes; gap junction; purinergic