H+ and Confined Water in Gating in Many Voltage-Gated Potassium Channels: Ion/Water/Counterion/Protein Networks and Protons Added to Gate the Channel
Abstract
1. Introduction
2. Major Topics
- (1)
- The Hv1 channel as an analogue of the VSD.
- (2)
- There is evidence from sodium channels that gating is slowed by D2O.
- (3)
- Certain mutations in the gate region make a huge difference.
- (4)
- Proton concentrations at the gate can be very high.
- (5)
- Wallace and coworkers found, in a bacterial sodium channel, NavAb, that hinge motions of the pore helix S6 and the C-terminal domain were involved with gating, but not S4 motion.
- (6)
- T1, the intracellular segment of the channel protein, matters.
- (7)
- The piquito, a brief pulse at the start of the channel opening sequence—proton tunneling?
- (8)
- Much of the evidence for the standard mechanical model is derived from experiments in which arginine was swapped for cysteine.
- (9)
- Other residues could be mutated as well.
- (10)
- The interactions that exist in the gate include ion–ion and hydrogen bonds.
- (11)
- Many molecular dynamics calculations on ion channels have been published.
- (12)
- Confined water, especially in channels.
- (13)
- Hydration dynamics.
- (14)
- In addition to the prolines at the gate, there is another class of conserved residues.
- (15)
- The EAG channels are also potassium channels.
- (16)
- Vibrations and rotations.
- (17)
- Thermodynamic behavior.
- (18)
- The probable importance of protons.
- (19)
- Experiments that appear to be more consistent with the standard model.
- (20)
- Energetics.
- (21)
- Omissions from this review.
2.1. The Hv1 Channel as an Analogue of the VSD
2.2. There Is Evidence from Sodium Channels That Gating Was Slowed by D2O [24,25,26]
2.3. Certain Mutations in the Gate Region Make a Huge Difference
2.4. Proton Concentration at the Gate Can Be Very High
2.5. Wallace and Coworkers Found, in a Bacterial Sodium Channel, NavAb, That Hinge Motions of the Pore Helix S6 and the C-Terminal Domain Were Involved with Gating, but Not S4 Motion
2.6. T1, the Intracellular Segment of the Channel Protein, Matters
2.7. The Piquito, a Brief Pulse at the Start of the Channel Opening Sequence—Proton Tunneling?
2.8. Much of the Evidence for the Standard Mechanical Model Is Derived from Experiments in Which Arginine Was Swapped for Cysteine
2.9. Other Residues Could Be Mutated as Well
2.10. The Interactions That Exist in the Gate Include Ion–Ion and Hydrogen Bonds
2.11. Many Molecular Dynamics Calculations on Ion Channels Have Been Published
2.12. Confined Water, Especially in Channels
2.13. Hydration Dynamics
2.14. In Addition to the Prolines at the Gate, There Is Another Class of Conserved Residues
2.15. The EAG Channels Are Also Potassium Channels
2.16. Vibrations and Rotations
2.17. Thermodynamic Behavior
2.18. The Probable Importance of Protons
2.19. Experiments That Appear to Be More Consistent with the Standard Model
2.20. Energetics
2.21. Omissions from This Review
3. Summary
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Channel | Amino Acids—Residue Number | pdb Code |
---|---|---|
Kv1.2 | N-412; S-411; N-414 | 3Lut |
Kv2.1 | S413; N410; S413 (next domain) | 8SD3 |
Shaker | N480; S479; N482 | 7SIP |
Hv1 | Q219; S215; Q98 | 3WKV |
Y157; D170; R207 | ||
Bacteriorhodopsin | Y57; R82; Q194 | 1FBB |
Y185; W86; R212 |
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Kariev, A.M.; Green, M.E. H+ and Confined Water in Gating in Many Voltage-Gated Potassium Channels: Ion/Water/Counterion/Protein Networks and Protons Added to Gate the Channel. Int. J. Mol. Sci. 2025, 26, 7325. https://doi.org/10.3390/ijms26157325
Kariev AM, Green ME. H+ and Confined Water in Gating in Many Voltage-Gated Potassium Channels: Ion/Water/Counterion/Protein Networks and Protons Added to Gate the Channel. International Journal of Molecular Sciences. 2025; 26(15):7325. https://doi.org/10.3390/ijms26157325
Chicago/Turabian StyleKariev, Alisher M., and Michael E. Green. 2025. "H+ and Confined Water in Gating in Many Voltage-Gated Potassium Channels: Ion/Water/Counterion/Protein Networks and Protons Added to Gate the Channel" International Journal of Molecular Sciences 26, no. 15: 7325. https://doi.org/10.3390/ijms26157325
APA StyleKariev, A. M., & Green, M. E. (2025). H+ and Confined Water in Gating in Many Voltage-Gated Potassium Channels: Ion/Water/Counterion/Protein Networks and Protons Added to Gate the Channel. International Journal of Molecular Sciences, 26(15), 7325. https://doi.org/10.3390/ijms26157325