The primary voltage sensor of the sodium channel is comprised of four positively charged S4 segments that mainly differ in the number of charged residues and are expected to contribute differentially to the gating process. To understand their kinetic and steady-state behavior, the fluorescence signals from the sites proximal to each of the four S4 segments of a rat skeletal muscle sodium channel were monitored simultaneously with either gating or ionic currents. At least one of the kinetic components of fluorescence from every S4 segment correlates with movement of gating charge. The fast kinetic component of fluorescence from sites S216C (S4 domain I), S660C (S4 domain II), and L1115C (S4 domain III) is comparable to the fast component of gating currents. In contrast, the fast component of fluorescence from the site S1436C (S4 domain IV) correlates with the slow component of gating. In all the cases, the slow component of fluorescence does not have any apparent correlation with charge movement. The fluorescence signals from sites reflecting the movement of S4s in the first three domains initiate simultaneously, whereas the fluorescence signals from the site S1436C exhibit a lag phase. These results suggest that the voltage-dependent movement of S4 domain IV is a later step in the activation sequence. Analysis of equilibrium and kinetic properties of fluorescence over activation voltage range indicate that S4 domain III is likely to move at most hyperpolarized potentials, whereas the S4s in domain I and domain II move at more depolarized potentials. The kinetics of fluorescence changes from sites near S4-DIV are slower than the activation time constants, suggesting that the voltage-dependent movement of S4-DIV may not be a prerequisite for channel opening. These experiments allow us to map structural features onto the kinetic landscape of a sodium channel during activation.
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1 November 2002
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October 29 2002
Tracking Voltage-dependent Conformational Changes in Skeletal Muscle Sodium Channel during Activation
Baron Chanda,
Baron Chanda
Department of Physiology and Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095
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Francisco Bezanilla
Francisco Bezanilla
Department of Physiology and Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095
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Baron Chanda
Department of Physiology and Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095
Francisco Bezanilla
Department of Physiology and Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095
Address correspondence to Dr. Francisco Bezanilla, Department of Physiology, David Geffen School of Medicine at UCLA, 10833 LeConte Ave., Los Angeles, CA 90095. Fax: (310) 794-9612; E-mail: [email protected]
Received:
July 22 2002
Revision Received:
September 11 2002
Accepted:
September 13 2002
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2002
J Gen Physiol (2002) 120 (5): 629–645.
Article history
Received:
July 22 2002
Revision Received:
September 11 2002
Accepted:
September 13 2002
Citation
Baron Chanda, Francisco Bezanilla; Tracking Voltage-dependent Conformational Changes in Skeletal Muscle Sodium Channel during Activation . J Gen Physiol 1 November 2002; 120 (5): 629–645. doi: https://doi.org/10.1085/jgp.20028679
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