Control of ionic selectivity by a pore helix residue in the Kv1.2 channel

Chao, Chia‐Chia; Huang, Chieh-Chen; Kuo, Chang-Shin; Leung, Yuk‐Man

doi:10.1007/s12576-010-0111-1

Cited by 5 publications

(2 citation statements)

References 13 publications

(28 reference statements)

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“…Together, these findings suggest that even sites at a distance from the selectivity filter can alter its static and dynamic properties. Interactions between the selectivity filter and adjacent domains are crucial determinants of C-type inactivation and ionic selectivity in potassium channels (35)(36)(37)(38)(39). Alkaline pH has been shown to cause functional "dilation" of the pore of TRPV5 through mechanisms apparently involving the pore helix (40).…”

Section: Discussionmentioning

confidence: 99%

Role of the Outer Pore Domain in Transient Receptor Potential Vanilloid 1 Dynamic Permeability to Large Cations

Munns¹,

Chung

Sánchez

et al. 2015

Journal of Biological Chemistry

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Background:The TRPV1 ion channel alters its ionic selectivity in an activity-dependent manner. Results: Mutations in multiple subregions of the TRPV1 pore selectively augment or reduce large cation permeability changes. Conclusion: Side chain identities within the pore shape conformational changes underlying dynamic ionic selectivity. Significance: Understanding TRPV1 dynamic ionic selectivity will provide crucial insight into channel activation and nociceptive signaling.

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Section: Discussionmentioning

confidence: 99%

Role of the Outer Pore Domain in Transient Receptor Potential Vanilloid 1 Dynamic Permeability to Large Cations

Munns¹,

Chung

Sánchez

et al. 2015

Journal of Biological Chemistry

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“…We had previously reported that mutations in the critical position 42 in Kcv NTS , which is equivalent to a functional hot spot for filter gating in KcsA (E71), MthK (V55), and Kv channels (V370 in Kv1.2 [ Chao et al, 2010 ]), alter key properties of this Kcv channel. In particular, the S42T mutant shows an increase in unitary conductance as well as a stabilization of the SF gate at hyperpolarizing voltages ( Rauh et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

Mutation in pore-helix modulates interplay between filter gate and Ba2+ block in a Kcv channel pore

Tewes,

Kubitzki,

Bytyqi

et al. 2024

Journal of General Physiology

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The selectivity filter of K+ channels catalyzes a rapid and highly selective transport of K+ while serving as a gate. To understand the control of this filter gate, we use the pore-only K+ channel KcvNTS in which gating is exclusively determined by the activity of the filter gate. It has been previously shown that a mutation at the C-terminus of the pore-helix (S42T) increases K+ permeability and introduces distinct voltage-dependent and K+-sensitive channel closures at depolarizing voltages. Here, we report that the latter are not generated by intrinsic conformational changes of the filter gate but by a voltage-dependent block caused by nanomolar trace contaminations of Ba2+ in the KCl solution. Channel closures can be alleviated by extreme positive voltages and they can be completely abolished by the high-affinity Ba2+ chelator 18C6TA. By contrast, the same channel closures can be augmented by adding Ba2+ at submicromolar concentrations to the cytosolic buffer. These data suggest that a conservative exchange of Ser for Thr in a crucial position of the filter gate increases the affinity of the filter for Ba2+ by >200-fold at positive voltages. While Ba2+ ions apparently remain only for a short time in the filter-binding sites of the WT channel before passing the pore, they remain much longer in the mutant channel. Our findings suggest that the dwell times of permeating and blocking ions in the filter-binding sites are tightly controlled by interactions between the pore-helix and the selectivity filter.

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Differential binding of monovalent cations to KcsA: Deciphering the mechanisms of potassium channel selectivity

Montoya¹,

Renart²,

Giudici³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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This work explores whether the ion selectivity and permeation properties of a model potassium channel, KcsA, could be explained based on ion binding features. Non-permeant Na or Li bind with low affinity (millimolar K's) to a single set of sites contributed by the S1 and S4 sites seen at the selectivity filter in the KcsA crystal structure. Conversely, permeant K, Rb, Tl and even Cs bind to two different sets of sites as their concentration increases, consistent with crystallographic evidence on the ability of permeant species to induce concentration-dependent transitions between conformational states (non-conductive and conductive) of the channel's selectivity filter. The first set of such sites, assigned also to the crystallographic S1 and S4 sites, shows similarly high affinities for all permeant species (micromolar K's), thus, securing displacement of potentially competing non-permeant cations. The second set of sites, available only to permeant cations upon the transition to the conductive filter conformation, shows low affinity (millimolar K's), thus, favoring cation dissociation and permeation and results from the contribution of all S1 through S4 crystallographic sites. The differences in affinities between permeant and non-permeant cations and the similarities in binding behavior within each of these two groups, correlate fully with their permeabilities relative to K, suggesting that binding is an important determinant of the channel's ion selectivity. Conversely, the complexity observed in permeation features cannot be explained just in terms of binding and likely relates to reported differences in the occupancy of the S2 and S3 sites by the permeant cations.

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Control of ionic selectivity by a pore helix residue in the Kv1.2 channel

Cited by 5 publications

References 13 publications

Role of the Outer Pore Domain in Transient Receptor Potential Vanilloid 1 Dynamic Permeability to Large Cations

Role of the Outer Pore Domain in Transient Receptor Potential Vanilloid 1 Dynamic Permeability to Large Cations

Mutation in pore-helix modulates interplay between filter gate and Ba2+ block in a Kcv channel pore

Differential binding of monovalent cations to KcsA: Deciphering the mechanisms of potassium channel selectivity

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