S-glutathionylation of ion channels: insights into the regulation of channel functions, thiol modification crosstalk, and mechanosensing

Antioxid Redox Signal. 2014 Feb 20;20(6):937-51. doi: 10.1089/ars.2013.5483. Epub 2013 Aug 20.


Significance: Ion channels control membrane potential, cellular excitability, and Ca(++) signaling, all of which play essential roles in cellular functions. The regulation of ion channels enables cells to respond to changing environments, and post-translational modification (PTM) is one major regulation mechanism.

Recent advances: Many PTMs (e.g., S-glutathionylation, S-nitrosylation, S-palmitoylation, S-sulfhydration, etc.) targeting the thiol group of cysteine residues have emerged to be essential for ion channels regulation under physiological and pathological conditions.

Critical issues: Under oxidative stress, S-glutathionylation could be a critical PTM that regulates many molecules. In this review, we discuss S-glutathionylation-mediated structural and functional changes of ion channels. Criteria for testing S-glutathionylation, methods and reagents used in ion channel S-glutathionylation studies, and thiol modification crosstalk, are also covered. Mechanotransduction, and S-glutathionylation of the mechanosensitive KATP channel, are discussed.

Future directions: Further investigation of the ion channel S-glutathionylation, especially the physiological significance of S-glutathionylation and thiol modification crosstalk, could lead to a better understanding of the thiol modifications in general and the ramifications of such modifications on cellular functions and related diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Mechanotransduction, Cellular / physiology*
  • Reactive Oxygen Species / metabolism
  • Sarcoplasmic Reticulum / metabolism
  • Signal Transduction / physiology
  • Sulfhydryl Compounds / metabolism*


  • Reactive Oxygen Species
  • Sulfhydryl Compounds