Aim: 

To assess the possibility than chondroitin 4- and/or 6- sulfate (CS4 and CS6), by their ability to bind extracellular calcium, could alter the gating properties of voltage-dependent ion channels via the Gouy-Chapman-Stern theory of the "surface screening effect".

Methods: 

Calcium binding capability of CS4 and CS6 solutions has been quantified by atomic absorbance flame spectrometry. The h channel and the voltage-dependent calcium channel of Xenopus laevis rod photoreceptors have been challenged with different concentrations of CS4 and CS6 and their activation curves fitted to Boltzman equations. Retinal chondroitins have been assayed and quantified in retinas by PAGEFS and HPLC analysis after digestion and AMAC-derivatization. Mouse DRG cultures were probed with Alcian blue staining and PAGEFS analysis.

Results: 

CS4 binds significantly more calcium than CS6, and is able to shift the activation curve of both currents by about -10 mV to the left, compatibly with the surface screening effect. CS6 perfusion not only shifts the activation curve to the left of about -7 mV, but also changes the voltage sensitivity of activation. Dose-effect of CS4 on the rod calcium current shows that CS4 is able to significantly shift the activation curve even at low concentrations, like the one we directly measured in the retina. In DRG cultures, neurones and glial cells differently express CS4 and CS6.

Conclusion: 

Our data show that chondroitins are able to influence the gating behaviour of ion channels, thus possibly modulating the function of the cell in physiological or pathological conditions when the extracellular matrix undergoes rearrangement following traumatic or inflammatory injuries.