The RCK2 domain uses a coordination site present in Kir channels to confer sodium sensitivity to Slo2.2 channels

Zhe Zhang, Avia Rosenhouse-Dantsker, Qiong Yao Tang, Sergei Noskov, Diomedes E. Logothetis

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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 channels 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.

Original languageEnglish
Pages (from-to)7554-7562
Number of pages9
JournalJournal of Neuroscience
Volume30
Issue number22
DOIs
StatePublished - 2 Jun 2010
Externally publishedYes

Fingerprint

Dive into the research topics of 'The RCK2 domain uses a coordination site present in Kir channels to confer sodium sensitivity to Slo2.2 channels'. Together they form a unique fingerprint.

Cite this