Sci. Signal., 26 July 2011
Channels Insight into the Sodium Channel
Elizabeth M. Adler
Science Signaling, AAAS, Washington, DC 20005, USA
Voltage-gated sodium channels open in response to small changes in the potential difference across the plasma membrane, enabling the influx of positively charged sodium ions, further membrane depolarization, and the propagation of action potentials in excitable cells. Like other voltage-gated ion channels, voltage-gated sodium channels have a tetrameric structure comprising four subunits (or subunit-like domains) around a central pore, with the voltage-sensing domains distinct from the pore-forming regions (see Horn). Payandeh et al. now describe the 2.7 Å resolution crystal structure of NavAb, a voltage-gated sodium channel from the bacterium Arcobacter butzleri, providing insight into various aspects of sodium channel function, including its voltage-dependent gating, selectivity for sodium, and blockade by drugs. NavAb, which the authors crystallized in a lipid-based bicelle system, was captured in a conformation in which the pore was closed but the four voltage-sensing S4 segments were in an outward activated conformation. The selectivity filter was short and water-filled and appears to enable the selective permeation of sodium ions through a mechanism that involves their partial dehydration as they pass through a high-field-strength anionic site provided by a ring of four Glu side chains. Unexpectedly, the NavAb structure revealed four "fenestrations," lateral openings that allowed acyl chains of lipids to penetrate the central cavity of the closed pore. The authors postulate that these fenestrations may provide routes for the entry of small hydrophobic drugs, giving them access to binding sites within the pore of the closed channel.
J. Payandeh, T. Scheuer, N. Zheng, W. A. Catterall, The crystal structure of a voltage-gated sodium channel. Nature 475, 353–358 (2011). [PubMed]
R. Horn, Peering into the spark of life. Nature 475, 305–306 (2011). [PubMed]
Citation: E. M. Adler, Insight into the Sodium Channel. Sci. Signal. 4, ec207 (2011).
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