title: Chondroitin sulfates act as extracellular gating modifiers on voltage-dependent ion channels.
abstract: OBJECTIVE
  Chondroitin sulfates are glycosaminoglycans bound to core proteins of proteoglycans in the extracellular matrix and perineuronal nets surrounding many types of neurones. Chondroitin 4- and chondroitin 6- sulfate can bind calcium ions with different affinities, depending on their sulfation position. Extracellular calcium plays a key role in determining the transmembrane potential sensed by voltage-operated ion channels (VOCs) by means of the "surface screening effect" theory (Gouy-Chapman-Stern theory). We wanted to test whether chondroitin sulfates at physiological concentration can effectively modulate the gating properties of VOCs.
  
  
  METHODS
  We recorded in patch-clamp experiments the shift of h and voltage-dependent calcium currents activation curves of Xenopus laevis photoreceptors perfused with chondroitin sulfate solutions in physiological extracellular calcium concentration.
  
  
  RESULTS
  We found that chondroitin 4- and 6- sulfate, with different capabilities, can shift the activation curve of h and voltage-dependent calcium channels, compatibly with the surface screening effect theory.
  
  
  CONCLUSIONS
  We conclude that chondroitin sulfates can alter VOCs gating by modulating the calcium concentration in the extracellular microenvironment. This phenomenon may explain why alterations in the chondroitin sulfation and abundance in the extracellular matrix are found along with altered neuronal function in pathological conditions.
authors.affiliation: 1Università dell'Insubria, Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Varese, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Vigetti
authors.forename: Olga
authors.initials: O
authors.lastname: Andrini
authors.forename: Moira
authors.initials: M
authors.lastname: Clerici
authors.forename: Daniela
authors.initials: D
authors.lastname: Negrini
authors.forename: Alberto
authors.initials: A
authors.lastname: Passi
authors.forename: Andrea
authors.initials: A
authors.lastname: Moriondo