1. Cell glycosaminoglycans content modulates human voltage-gated proton channel (H V 1) gating.
- Author
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Orts DJB and Arcisio-Miranda M
- Subjects
- Animals, CHO Cells, Chondroitin Sulfates, Cricetinae, Cricetulus, Glycosaminoglycans, Heparitin Sulfate, Humans, Male, Ion Channel Gating physiology, Protons
- Abstract
Voltage-gated proton channels (H
V 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 HV 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 HV 1 N-terminal truncated isoforms expressed in wild-type CHO-K1 and CHO-745 cells. On three different monomeric HV 1 constructs, no alterations in the biophysical parameters were observed. Moreover, we have shown that HV 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 HV 1 channel., (© 2021 Federation of European Biochemical Societies.)- Published
- 2022
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