Cell glycosaminoglycans content modulates human voltage-gated proton channel (H 1) gating.

Voltage-gated proton channels (H 1) have been found in many mammalian cells and play a crucial role in the immune system, male fertility, and cancer progression. Glycosaminoglycans play a significant role in various aspects of cell physiology, including the modulation of membrane receptors and ion channel function. We present here evidence that mechanosensitivity of the dimeric H 1 channel transduce changes on cell membrane fluidity related to the defective biosynthesis of chondroitin sulfate and heparan sulfate in Chinese Hamster Ovary (CHO-745) cells into a leftward shift in the activation voltage dependence. This effect was accompanied by an increase in the H current, and an acceleration of the activation kinetics, under symmetrical or asymmetrical pH gradient (ΔpH) conditions. Similar gating alterations were evoked by two naturally occurring H 1 N-terminal truncated isoforms expressed in wild-type CHO-K1 and CHO-745 cells. On three different monomeric H 1 constructs, no alterations in the biophysical parameters were observed. Moreover, we have shown that H 1 gating can be modulated by manipulating CHO-K1 cell membrane fluidity. Our results suggest that the defective biosynthesis of chondroitin sulfate and heparan sulfate on CHO-745 cell increases membrane fluidity and allosterically modulates the coupling between voltage- and ΔpH-sensing through the dimeric H 1 channel.