Mechanosensitive Gating of Kv Channels
K-selective voltage-gated channels (Kv) are multi-conformation bilayer-embedded proteins whose mechanosensitive (MS) Popen(V) implies that at least one conformational transition requires the restructuring of the channel-bilayer interface. Unlike Morris and colleagues, who attributed MS-Kv responses...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332674/ |
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pubmed-43326742015-02-24 Mechanosensitive Gating of Kv Channels Morris, Catherine E. Prikryl, Emil A. Joós, Béla Research Article K-selective voltage-gated channels (Kv) are multi-conformation bilayer-embedded proteins whose mechanosensitive (MS) Popen(V) implies that at least one conformational transition requires the restructuring of the channel-bilayer interface. Unlike Morris and colleagues, who attributed MS-Kv responses to a cooperative V-dependent closed-closed expansion↔compaction transition near the open state, Mackinnon and colleagues invoke expansion during a V-independent closed↔open transition. With increasing membrane tension, they suggest, the closed↔open equilibrium constant, L, can increase >100-fold, thereby taking steady-state Popen from 0→1; “exquisite sensitivity to small…mechanical perturbations”, they state, makes a Kv “as much a mechanosensitive…as…a voltage-dependent channel”. Devised to explain successive g K (V) curves in excised patches where tension spontaneously increased until lysis, their L-based model falters in part because of an overlooked IK feature; with recovery from slow inactivation factored in, their g(V) datasets are fully explained by the earlier model (a MS V-dependent closed-closed transition, invariant L≥4). An L-based MS-Kv predicts neither known Kv time courses nor the distinctive MS responses of Kv-ILT. It predicts Kv densities (hence gating charge per V-sensor) several-fold different from established values. If opening depended on elevated tension (L-based model), standard g K (V) operation would be compromised by animal cells’ membrane flaccidity. A MS V-dependent transition is, by contrast, unproblematic on all counts. Since these issues bear directly on recent findings that mechanically-modulated Kv channels subtly tune pain-related excitability in peripheral mechanoreceptor neurons we undertook excitability modeling (evoked action potentials). Kvs with MS V-dependent closed-closed transitions produce nuanced mechanically-modulated excitability whereas an L-based MS-Kv yields extreme, possibly excessive (physiologically-speaking) inhibition. Public Library of Science 2015-02-13 /pmc/articles/PMC4332674/ /pubmed/25680191 http://dx.doi.org/10.1371/journal.pone.0118335 Text en © 2015 Morris et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Morris, Catherine E. Prikryl, Emil A. Joós, Béla |
| spellingShingle |
Morris, Catherine E. Prikryl, Emil A. Joós, Béla Mechanosensitive Gating of Kv Channels |
| author_facet |
Morris, Catherine E. Prikryl, Emil A. Joós, Béla |
| author_sort |
Morris, Catherine E. |
| title |
Mechanosensitive Gating of Kv Channels |
| title_short |
Mechanosensitive Gating of Kv Channels |
| title_full |
Mechanosensitive Gating of Kv Channels |
| title_fullStr |
Mechanosensitive Gating of Kv Channels |
| title_full_unstemmed |
Mechanosensitive Gating of Kv Channels |
| title_sort |
mechanosensitive gating of kv channels |
| description |
K-selective voltage-gated channels (Kv) are multi-conformation bilayer-embedded proteins whose mechanosensitive (MS) Popen(V) implies that at least one conformational transition requires the restructuring of the channel-bilayer interface. Unlike Morris and colleagues, who attributed MS-Kv responses to a cooperative V-dependent closed-closed expansion↔compaction transition near the open state, Mackinnon and colleagues invoke expansion during a V-independent closed↔open transition. With increasing membrane tension, they suggest, the closed↔open equilibrium constant, L, can increase >100-fold, thereby taking steady-state Popen from 0→1; “exquisite sensitivity to small…mechanical perturbations”, they state, makes a Kv “as much a mechanosensitive…as…a voltage-dependent channel”. Devised to explain successive g
K
(V) curves in excised patches where tension spontaneously increased until lysis, their L-based model falters in part because of an overlooked IK feature; with recovery from slow inactivation factored in, their g(V) datasets are fully explained by the earlier model (a MS V-dependent closed-closed transition, invariant L≥4). An L-based MS-Kv predicts neither known Kv time courses nor the distinctive MS responses of Kv-ILT. It predicts Kv densities (hence gating charge per V-sensor) several-fold different from established values. If opening depended on elevated tension (L-based model), standard g
K
(V) operation would be compromised by animal cells’ membrane flaccidity. A MS V-dependent transition is, by contrast, unproblematic on all counts. Since these issues bear directly on recent findings that mechanically-modulated Kv channels subtly tune pain-related excitability in peripheral mechanoreceptor neurons we undertook excitability modeling (evoked action potentials). Kvs with MS V-dependent closed-closed transitions produce nuanced mechanically-modulated excitability whereas an L-based MS-Kv yields extreme, possibly excessive (physiologically-speaking) inhibition. |
| publisher |
Public Library of Science |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332674/ |
| _version_ |
1613189870885273600 |