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The RCK2 Domain Uses a Coordination Site Present in Kir Channels to Confer Sodium Sensitivity to Slo2.2 Channels

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Title: The RCK2 Domain Uses a Coordination Site Present in Kir Channels to Confer Sodium Sensitivity to Slo2.2 Channels
Author(s): Zhang, Zhe; Rosenhouse-Dantsker, Avia; Tang, Qiong-Yao; Noskov, Sergei; Logothetis, Diomedes E
Subject(s): potassium channels sodium sensitivity
Abstract: Slo2 Na+-activated potassium channels are widely expressed in neurons and other cells, such as kidney, heart, and skeletal muscle. Although their important physiological roles continue to be appreciated, molecular determinants responsible for sensing intracellular Na+ remain unknown. Here we report identification of an Na+ regulatory site, similar to an Na+ coordination motif described in Kir channels, localized in the RCK2 domain of Slo2.2 channels. Molecular simulations of the homology-modeled Slo2.2 RCK2 domain provided structural insights into the organization of this Na+ coordination site. Furthermore, free energy calculations reproduced the experimentally derived monovalent cation selectivity. Our results suggest that Slo2.2 and Kir hannels share a similar mechanism to coordinate Na+. The localization of an Na+ sensor within the RCK2 domain of Slo2.2 further supports the role of RCK (regulators of conductance of K+) domains of Slo channels in coupling ion sensing to channel gating.
Issue Date: 2010-06-02
Publisher: Society for Neuroscience
Citation Info: Zhang, Z., Rosenhouse-Dantsker, A., Tang, Q. Y., Noskov, S., & Logothetis, D. E. 2010. The RCK2 Domain Uses a Coordination Site Present in Kir Channels to Confer Sodium Sensitivity to Slo2.2 Channels. Journal of Neuroscience, 30(22): 7554-7562. DOI: 10.1523/JNEUROSCI.0525-10.2010
Type: Article
Description: The original source for this publication is at the Society for Neuroscience; DOI: 10.1523/JNEUROSCI.0525-10.2010
URI: http://hdl.handle.net/10027/7587
ISSN: 0270-6474
Sponsor: Z.Z. was supported by American Heart Association Grant 09SDG2290002. D.E.L. was supported by National Institutes of Health Grants HL059949-11 and HL090882-01. S.N. was supported by Canadian Institutes of Health Research (CIHR) Operating Grant MOP-186232.
Date Available in INDIGO: 2011-05-07
 

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