Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor
Whether ion channel gating is independent of ion permeation has been an enduring, unresolved question. Here, applying single channel recording to the archetypal muscle nicotinic receptor, we unmask coupling between channel gating and ion permeation by structural perturbation of a conserved intramemb...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-04-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/66225 |
| _version_ | 1811237011097387008 |
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| author | John R Strikwerda Steven M Sine |
| author_facet | John R Strikwerda Steven M Sine |
| author_sort | John R Strikwerda |
| collection | DOAJ |
| description | Whether ion channel gating is independent of ion permeation has been an enduring, unresolved question. Here, applying single channel recording to the archetypal muscle nicotinic receptor, we unmask coupling between channel gating and ion permeation by structural perturbation of a conserved intramembrane salt bridge. A charge-neutralizing mutation suppresses channel gating, reduces unitary current amplitude, and increases fluctuations of the open channel current. Power spectra of the current fluctuations exhibit low- and high-frequency Lorentzian components, which increase in charge-neutralized mutant receptors. After aligning channel openings and closings at the time of transition, the average unitary current exhibits asymmetric relaxations just after channel opening and before channel closing. A theory in which structural motions contribute jointly to channel gating and ion conduction describes both the power spectrum and the current relaxations. Coupling manifests as a transient increase in the open channel current upon channel opening and a decrease upon channel closing. |
| first_indexed | 2024-04-12T12:17:47Z |
| format | Article |
| id | doaj.art-648ebdb8c8b64fa29fc79ccf1b83a224 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:17:47Z |
| publishDate | 2021-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-648ebdb8c8b64fa29fc79ccf1b83a2242022-12-22T03:33:22ZengeLife Sciences Publications LtdeLife2050-084X2021-04-011010.7554/eLife.66225Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptorJohn R Strikwerda0https://orcid.org/0000-0001-6155-7919Steven M Sine1https://orcid.org/0000-0002-0594-6052Receptor Biology Laboratory, Department of Physiology and Biomedical Engineering, Rochester, United StatesReceptor Biology Laboratory, Department of Physiology and Biomedical Engineering, Rochester, United States; Department of Molecular Pharmacology and Experimental Therapeutics, Rochester, United States; Department of Neurology, Mayo Clinic College of Medicine, Rochester, United StatesWhether ion channel gating is independent of ion permeation has been an enduring, unresolved question. Here, applying single channel recording to the archetypal muscle nicotinic receptor, we unmask coupling between channel gating and ion permeation by structural perturbation of a conserved intramembrane salt bridge. A charge-neutralizing mutation suppresses channel gating, reduces unitary current amplitude, and increases fluctuations of the open channel current. Power spectra of the current fluctuations exhibit low- and high-frequency Lorentzian components, which increase in charge-neutralized mutant receptors. After aligning channel openings and closings at the time of transition, the average unitary current exhibits asymmetric relaxations just after channel opening and before channel closing. A theory in which structural motions contribute jointly to channel gating and ion conduction describes both the power spectrum and the current relaxations. Coupling manifests as a transient increase in the open channel current upon channel opening and a decrease upon channel closing.https://elifesciences.org/articles/66225ligand gated ion channelssingle channel recordingopen channel fluctuations |
| spellingShingle | John R Strikwerda Steven M Sine Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor eLife ligand gated ion channels single channel recording open channel fluctuations |
| title | Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor |
| title_full | Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor |
| title_fullStr | Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor |
| title_full_unstemmed | Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor |
| title_short | Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor |
| title_sort | unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor |
| topic | ligand gated ion channels single channel recording open channel fluctuations |
| url | https://elifesciences.org/articles/66225 |
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