Oxidation and reduction control of the inactivation gating of Torpedo CIC-0 chloride channels

Yong Li, Wei Ping Yu, Chia Wei Lin, Tsung-Yu Chen

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14 Scopus citations

Abstract

Oxidation and reduction (redox) are known to modulate the function of a variety of ion channels. Here, we report a redox regulation of the function of CIC-0, a chloride (Cl-) channel from the Torpedo electric organ. The study was motivated by the occasional observation of oocytes with hyperpolarization-activated Cl- current when these oocytes expressed CIC-0. We find that these atypical recording traces can be turned into typical CIC-0 current by incubating the oocyte in millimolar concentrations of reducing agents, suggesting that the channel function is regulated by oxidation and reduction. The redox control apparently results from an effect of oxidation on the slow (inactivation) gating: oxidation renders it more difficult for the channel to recover from the inactivated states. Introducing the point mutation C212S in CIC-0 suppresses the inactivation state, and this inactivation- suppressed mutant is no longer sensitive to the inhibition by oxidizing reagents. However, C212 is probably not the target for the redox reaction because the regulation of the inactivation gating by oxidation is still present in a pore mutant (K165C/K165 heterodimer) in which the C212S mutation is present. Taking advantage of the K165C/K165 heterodimer, we further explore the oxidation effect in CIC-0 by methane thiosulfonate (MTS) modifications. We found that trimethylethylammonium MTS modification of the introduced cysteine can induce current in the K165C/K165 heterodimer, an effect attributed to the recovery of the channel from the inactivation state. The current induction by MTS reagents is subjected to redox controls, and thus the extent of this current induction can serve as an indicator to report the oxidation state of the channel. These results together suggest that the inactivation gating of CIC-0 is affected by redox regulation. The finding also provides a convenient method to "cure" those atypical recording traces of CIC-0 expressed in Xenopus oocytes.

Original languageEnglish (US)
Pages (from-to)3936-3945
Number of pages10
JournalBiophysical Journal
Volume88
Issue number6
DOIs
StatePublished - Jun 2005

ASJC Scopus subject areas

  • Biophysics

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