Molecular determinants of coupling between the domain iii voltage sensor and pore of a sodium channel

ABSTRACT In a voltage-dependent sodium channel, the activation of voltage sensors upon depolarization leads to the opening of the pore gates. To elucidate the principles underlying this

conformational coupling, we investigated a putative gating interface in domain III of the sodium channel using voltage-clamp fluorimetry and tryptophan-scanning mutagenesis. Most mutations

have similar energetic effects on voltage-sensor activation and pore opening. However, several mutations stabilized the activated voltage sensor while concurrently destabilizing the open

pore. When mapped onto a homology model of the sodium channel, most localized to hinge regions of the gating interface. Our analysis shows that these residues are involved in energetic

coupling of the voltage sensor to the pore when both are in resting and when both are in activated conformations, supporting the notion that electromechanical coupling in a voltage-dependent

ion channel involves the movement of rigid segments connected by elastic hinges. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ENERGY LANDSCAPE OF A KV CHANNEL REVEALED BY TEMPERATURE STEPS

WHILE PERTURBING ITS ELECTROMECHANICAL COUPLING Article Open access 09 April 2025 VOLTAGE SENSORS OF A NA+ CHANNEL DISSOCIATE FROM THE PORE DOMAIN AND FORM INTER-CHANNEL DIMERS IN THE

RESTING STATE Article Open access 19 December 2023 MULTIPLE MECHANISMS CONTRIBUTE TO FLUOROMETRY SIGNALS FROM THE VOLTAGE-GATED PROTON CHANNEL Article Open access 26 October 2022 REFERENCES

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generalized coordinates. _J. Struct. Chem._ 22, 4–8 (1981). Article  Google Scholar  Download references ACKNOWLEDGEMENTS This project was supported by funds from the US National Institutes

of Health (GM084140-01), the American Heart Association Scientist Development Award (0535214N) and the Shaw Scientist award to B.C. We thank M. Goldschen for help with preparing

Supplementary Figure 3, K. Schuldt for excellent technical assistance and the members of the Chanda laboratory for their comments and discussions. AUTHOR INFORMATION Author notes * Sandipan

Chowdhury Present address: Biophysics Graduate Training Program, University of Wisconsin, Madison, Wisconsin, USA * Yukiko Muroi Present address: Present address: Division of Allergy and

Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA., * Yukiko Muroi and Manoel Arcisio-Miranda: These authors contributed equally to this work.

AUTHORS AND AFFILIATIONS * Department of Physiology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA Yukiko Muroi, Manoel Arcisio-Miranda, Sandipan

Chowdhury & Baron Chanda Authors * Yukiko Muroi View author publications You can also search for this author inPubMed Google Scholar * Manoel Arcisio-Miranda View author publications You

can also search for this author inPubMed Google Scholar * Sandipan Chowdhury View author publications You can also search for this author inPubMed Google Scholar * Baron Chanda View author

publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Y.M. and M.A-.M. contributed equally to this work; Y.M. and M.A.-M. performed all the experiments and

analyzed the data; S.C. created the structural model; S.C. and B.C. generated the coupling models; Y.M., M.A.-M. and B.C. wrote the paper. CORRESPONDING AUTHOR Correspondence to Baron

Chanda. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–4,

Supplementary Tables 1 and 2, and Supplementary Methods (PDF 2066 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Muroi, Y., Arcisio-Miranda, M.,

Chowdhury, S. _et al._ Molecular determinants of coupling between the domain III voltage sensor and pore of a sodium channel. _Nat Struct Mol Biol_ 17, 230–237 (2010).

https://doi.org/10.1038/nsmb.1749 Download citation * Received: 16 June 2009 * Accepted: 06 November 2009 * Published: 31 January 2010 * Issue Date: February 2010 * DOI:

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