The voltage-sensing S4 segments in the sodium channel undergo conformational rearrangements in response to changes in the electric field. However, it remains unclear whether these structures move independently or in a coordinated manner. Previously, site-directed fluorescence measurements were shown to track S4 transitions in each of the four domains (Chanda, B., and F. Bezanilla. 2002. J. Gen. Physiol. 120:629–645). Here, using a similar technique, we provide direct evidence of coupling interactions between voltage sensors in the sodium channel. Pairwise interactions between S4s were evaluated by comparing site-specific conformational changes in the presence and absence of a gating perturbation in a distal domain. Reciprocity of effect, a fundamental property of thermodynamically coupled systems, was measured by generating converse mutants. The magnitude of a local gating perturbation induced by a remote S4 mutation depends on the coupling strength and the relative equilibrium positions of the two voltage sensors. In general, our data indicates that the movement of all four voltage sensors in the sodium channel are coupled to a varying extent. Moreover, a gating perturbation in S4-DI has the largest effect on the activation of S4-DIV and vice versa, demonstrating an energetic linkage between S4-DI and S4-DIV. This result suggests a physical mechanism by which the activation and inactivation process may be coupled in voltage-gated sodium channels. In addition, we propose that cooperative interactions between voltage sensors may be the mechanistic basis for the fast activation kinetics of the sodium channel.
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1 March 2004
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February 23 2004
Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements
Baron Chanda,
Baron Chanda
2Centro de Estudios Cientificos, Valdivia, Chile
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Osei Kwame Asamoah,
Osei Kwame Asamoah
1Departments of Physiology and Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, CA 90025
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Francisco Bezanilla
Francisco Bezanilla
1Departments of Physiology and Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, CA 90025
2Centro de Estudios Cientificos, Valdivia, Chile
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Baron Chanda
2Centro de Estudios Cientificos, Valdivia, Chile
Osei Kwame Asamoah
1Departments of Physiology and Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, CA 90025
Francisco Bezanilla
1Departments of Physiology and Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, CA 90025
2Centro de Estudios Cientificos, Valdivia, Chile
Address correspondence to Dr. Francisco Bezanilla, Departments of Physiology and Anesthesiology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Dr. South, Los Angeles, CA 90025. Fax: (310) 794-9612; email: [email protected]
Baron Chanda and Osei Kwame Asamoah contributed equally to this work.
Received:
November 03 2003
Accepted:
January 20 2004
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2004
J Gen Physiol (2004) 123 (3): 217–230.
Article history
Received:
November 03 2003
Accepted:
January 20 2004
Citation
Baron Chanda, Osei Kwame Asamoah, Francisco Bezanilla; Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements . J Gen Physiol 1 March 2004; 123 (3): 217–230. doi: https://doi.org/10.1085/jgp.200308971
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