Cell glycosaminoglycans content modulates human voltage‐gated proton channel (H V 1) gating

FEBS Journal ◽  
2021 ◽  
Author(s):  
Diego J. B. Orts ◽  
Manoel Arcisio‐Miranda
Keyword(s):  
Proton Channel ◽  
Voltage Gated

Voltage-gated proton channel is expressed on phagosome

2009 ◽  
Vol 65 ◽  
pp. S73
Author(s):  
Yoshifumi Okochi ◽  
Mari Sasaki ◽  
Yasushi Okamura
Keyword(s):  
Proton Channel ◽  
Voltage Gated

scholarly journals Onion (Allium cepa L.) peel extract (OPE) regulates human sperm motility via protein kinase C-mediated activation of the human voltage-gated proton channel

Andrology ◽  
2017 ◽  
Vol 5 (5) ◽  
pp. 979-989 ◽  
Author(s):  
M. R. Chae ◽  
S. J. Kang ◽  
K. P. Lee ◽  
B. R. Choi ◽  
H. K. Kim ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Allium Cepa ◽  
Sperm Motility ◽  
Human Sperm ◽  
Proton Channel ◽  
Voltage Gated ◽  
Kinase C ◽  
Allium Cepa L ◽  
Peel Extract

Microglial Voltage-Gated Proton Channel Hv1 in Ischemic Stroke

2013 ◽  
Vol 5 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Long-Jun Wu
Keyword(s):  
Ischemic Stroke ◽  
Proton Channel ◽  
Voltage Gated

scholarly journals Tryptophan 207 is crucial to the unique properties of the human voltage-gated proton channel, hHV1

2015 ◽  
Vol 146 (5) ◽  
pp. 343-356 ◽  
Author(s):  
Vladimir V. Cherny ◽  
Deri Morgan ◽  
Boris Musset ◽  
Gustavo Chaves ◽  
Susan M.E. Smith ◽  
...  
Keyword(s):  
Transmembrane Helix ◽  
Ph Sensor ◽  
Proton Channel ◽  
Tryptophan Residue ◽  
Ph Sensing ◽  
Ph Sensors ◽  
Voltage Gated ◽  
Karlodinium Veneficum ◽  
Channel Opening ◽  
External Ph

Part of the “signature sequence” that defines the voltage-gated proton channel (HV1) is a tryptophan residue adjacent to the second Arg in the S4 transmembrane helix: RxWRxxR, which is perfectly conserved in all high confidence HV1 genes. Replacing Trp207 in human HV1 (hHV1) with Ala, Ser, or Phe facilitated gating, accelerating channel opening by 100-fold, and closing by 30-fold. Mutant channels opened at more negative voltages than wild-type (WT) channels, indicating that in WT channels, Trp favors a closed state. The Arrhenius activation energy, Ea, for channel opening decreased to 22 kcal/mol from 30–38 kcal/mol for WT, confirming that Trp207 establishes the major energy barrier between closed and open hHV1. Cation–π interaction between Trp207 and Arg211 evidently latches the channel closed. Trp207 mutants lost proton selectivity at pHo >8.0. Finally, gating that depends on the transmembrane pH gradient (ΔpH-dependent gating), a universal feature of HV1 that is essential to its biological functions, was compromised. In the WT hHV1, ΔpH-dependent gating is shown to saturate above pHi or pHo 8, consistent with a single pH sensor with alternating access to internal and external solutions. However, saturation occurred independently of ΔpH, indicating the existence of distinct internal and external pH sensors. In Trp207 mutants, ΔpH-dependent gating saturated at lower pHo but not at lower pHi. That Trp207 mutation selectively alters pHo sensing further supports the existence of distinct internal and external pH sensors. Analogous mutations in HV1 from the unicellular species Karlodinium veneficum and Emiliania huxleyi produced generally similar consequences. Saturation of ΔpH-dependent gating occurred at the same pHo and pHi in HV1 of all three species, suggesting that the same or similar group(s) is involved in pH sensing. Therefore, Trp enables four characteristic properties: slow channel opening, highly temperature-dependent gating kinetics, proton selectivity, and ΔpH-dependent gating.

Voltage-gated proton channel is expressed on phagosomes

2009 ◽  
Vol 382 (2) ◽  
pp. 274-279 ◽  
Author(s):  
Yoshifumi Okochi ◽  
Mari Sasaki ◽  
Hirohide Iwasaki ◽  
Yasushi Okamura
Keyword(s):  
Proton Channel ◽  
Voltage Gated

Abstract T P229: Deletion of Voltage Gated Proton Channel in Microglial Cells is Neurovascular Protective After Ischemic Brain Injury

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Weiguo Li ◽  
Becca Ward ◽  
Mohammed Abdelsaid ◽  
Tianzheng Yu ◽  
Yisang Yoon ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Ischemia Reperfusion ◽  
Hemorrhagic Transformation ◽  
Artery Occlusion ◽  
Proton Channel ◽  
Ros Generation ◽  
Vascular Integrity ◽  
Voltage Gated ◽  
Underlying Mechanisms ◽  
Cerebral Artery Occlusion

Despite the failure of antioxidant treatments in clinical trials, the undoubted role of reactive oxygen species (ROS) in neurovascular damage after ischemic stroke calls for a more targeted approach. ROS production by microglia, the primary resident immune cells in the brain, is a key event of this process in ischemic stroke. Voltage gated proton channel, Hv1, is localized primarily to microglia and sustains NADPH oxidase activity. Deletion of Hv1 is neuroprotective after permanent middle cerebral artery occlusion (MCAO). We hypothesized that Hv1-mediated microglial ROS generation is also critical for vascular integrity and contributes to reperfusion injury after transient ischemic stroke. The wildtype (WT) and Hv1 knockout (KO) rats (n=4) were subjected to permanent or 3/24 h transient MCAO. The neurological deficiency, infarct, hemorrhagic transformation, and edema ratio were assessed. We found that in both permanent and transient MCAO model, KO rats develop smaller infarct, less vascular injury, edema, and hemorrhagic transformation, resulting in better short-term functional outcome. These results suggest that deletion of microglial Hv1 channel is vasculoprotective after ischemia/reperfusion and the underlying mechanisms need to be further studied.

Microglial Voltage-Gated Proton Channel Hv1 in Neurological Disorders

2021 ◽  
pp. 381-405
Author(s):  
Madhuvika Murugan ◽  
Long-Jun Wu
Keyword(s):  
Neurological Disorders ◽  
Proton Channel ◽  
Voltage Gated

scholarly journals Properties of the Voltage-Gated Proton Channel Gating Currents

2018 ◽  
Vol 114 (3) ◽  
pp. 546a ◽  
Author(s):  
Emerson M. Carmona ◽  
David Baez-Nieto ◽  
Amaury Pupo ◽  
Karen Castillo ◽  
Osvaldo Alvarez ◽  
...  
Keyword(s):  
Channel Gating ◽  
Proton Channel ◽  
Gating Currents ◽  
Voltage Gated

scholarly journals Hydrophobic gasket mutation produces gating pore currents in closed human voltage-gated proton channels

2019 ◽  
Vol 116 (38) ◽  
pp. 18951-18961 ◽  
Author(s):  
Richard Banh ◽  
Vladimir V. Cherny ◽  
Deri Morgan ◽  
Boris Musset ◽  
Sarah Thomas ◽  
...  
Keyword(s):  
Proton Channel ◽  
Voltage Gated ◽  
Closed State ◽  
Channel Opening ◽  
Proton Current ◽  
Voltage Dependent ◽  
Current Flows ◽  
Voltage Gated Ion Channels ◽  
Dynamics Simulations ◽  
Voltage Sensing Domain

The hydrophobic gasket (HG), a ring of hydrophobic amino acids in the voltage-sensing domain of most voltage-gated ion channels, forms a constriction between internal and external aqueous vestibules. Cationic Arg or Lys side chains lining the S4 helix move through this “gating pore” when the channel opens. S4 movement may occur during gating of the human voltage-gated proton channel, hHV1, but proton current flows through the same pore in open channels. Here, we replaced putative HG residues with less hydrophobic residues or acidic Asp. Substitution of individuals, pairs, or all 3 HG positions did not impair proton selectivity. Evidently, the HG does not act as a secondary selectivity filter. However, 2 unexpected functions of the HG in HV1 were discovered. Mutating HG residues independently accelerated channel opening and compromised the closed state. Mutants exhibited open–closed gating, but strikingly, at negative voltages where “normal” gating produces a nonconducting closed state, the channel leaked protons. Closed-channel proton current was smaller than open-channel current and was inhibited by 10 μM Zn2+. Extreme hyperpolarization produced a deeper closed state through a weakly voltage-dependent transition. We functionally identify the HG as Val109, Phe150, Val177, and Val178, which play a critical and exclusive role in preventing H+ influx through closed channels. Molecular dynamics simulations revealed enhanced mobility of Arg208 in mutants exhibiting H+ leak. Mutation of HG residues produces gating pore currents reminiscent of several channelopathies.

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