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Home / Equine Research Bank / J Gen Physiol / Redox regulation of large conductance Ca(2+)-activated K+ ch...
The Journal of general physiology1997; 110(1); 35-44; doi: 10.1085/jgp.110.1.35

Redox regulation of large conductance Ca(2+)-activated K+ channels in smooth muscle cells.

Abstract: The effects of sulfhydryl reduction/oxidation on the gating of large-conductance, Ca(2+)-activated K+ (maxi-K) channels were examined in excised patches from tracheal myocytes. Channel activity was modified by sulfhydryl redox agents applied to the cytosolic surface, but not the extracellular surface, of membrane patches. Sulfhydryl reducing agents dithiothreitol, beta-mercaptoethanol, and GSH augmented, whereas sulfhydryl oxidizing agents diamide, thimerosal, and 2,2'-dithiodipyridine inhibited, channel activity in a concentration-dependent manner. Channel stimulation by reduction and inhibition by oxidation persisted following washout of the compounds, but the effects of reduction were reversed by subsequent oxidation, and vice versa. The thiol-specific reagents N-ethylmaleimide and (2-aminoethyl)methanethiosulfonate inhibited channel activity and prevented the effect of subsequent sulfhydryl oxidation. Measurements of macroscopic currents in inside-out patches indicate that reduction only shifted the voltage/nP0 relationship without an effect on the maximum conductance of the patch, suggesting that the increase in nP0 following reduction did not result from recruitment of more functional channels but rather from changes of channel gating. We conclude that redox modulation of cysteine thiol groups, which probably involves thiol/disulfide exchange, alters maxi-K channel gating, and that this modulation likely affects channel activity under physiological conditions.
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Publication Date: 1997-07-01 PubMed ID: 9234169PubMed Central: PMC2229357DOI: 10.1085/jgp.110.1.35Google Scholar: Lookup
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  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigated the effects of redox (reduction/oxidation) treatments on the activity of a specific type of potassium channel in muscle cells. The study found that the application of certain redox agents to one specific area of these channels could either enhance or inhibit their activity, potentially impacting their function in muscle cells.

Study process and methodologies

  • The researchers studied large conductance, Ca(2+)-activated K+ (maxi-K) channels in tracheal myocytes, a type of muscle cell. They did this by examining excised patches from these cells.
  • They used a range of different redox agents applied to the cytosolic surface of the membrane patches. The agents applied were of two main types; sulfhydryl reducing agents like dithiothreitol, beta-mercaptoethanol, and GSH, and sulfhydryl oxidizing agents like diamide, thimerosal, and 2,2′-dithiodipyridine.
  • The researchers monitored changes in channel activity following the application of these redox agents, noting whether channel activity was increased or decreased in response.

Major findings

  • The researchers found that the channel activity was affected in a concentration-dependent manner by the redox agents, with sulfhydryl reducing agents augmenting channel activity and sulfhydryl oxidizing agents inhibiting it.
  • The effects of these redox agents persisted even after the compounds were washed out, with the effects of reduction being reversed by subsequent oxidation and vice versa.
  • The thiol-specific reagents used in the study inhibited channel activity and prevented subsequent sulfhydryl oxidation from affecting the channels.
  • Interestingly, macroscopic currents measured in the inside-out patches suggested that the redox agents only shifted the voltage/nP0 relationship without affecting the maximum conductance of the patch. This suggests that the increase in nP0 (an indicator of the number of channels open simultaneously) did not come from recruiting more functional channels but was caused by changes in the gating of the channels themselves.

Study conclusion

  • The findings of this study suggest that redox modulation of cysteine thiol groups, likely through the process of thiol/disulfide exchange, can affect the gating or functioning of maxi-K channels in muscle cells. This implies that changes in the redox status of these cells could affect the action of these channels and potentially impact the function of the muscle cells themselves.

Cite This Article

APA
Wang ZW, Nara M, Wang YX, Kotlikoff MI. (1997). Redox regulation of large conductance Ca(2+)-activated K+ channels in smooth muscle cells. J Gen Physiol, 110(1), 35-44. https://doi.org/10.1085/jgp.110.1.35

Publication

The Journal of general physiology
ISSN: 0022-1295
NlmUniqueID: 2985110R
Country: United States
Language: English
Volume: 110
Issue: 1
Pages: 35-44

Researcher Affiliations

Wang, Z W
  • Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Nara, M
    Wang, Y X
      Kotlikoff, M I

        MeSH Terms

        • Animals
        • Calcium / physiology
        • Cytosol / metabolism
        • Electric Conductivity
        • Ethyl Methanesulfonate / analogs & derivatives
        • Ethyl Methanesulfonate / pharmacology
        • Ethylmaleimide / pharmacology
        • Horses
        • Indicators and Reagents / pharmacology
        • Muscle, Smooth / cytology
        • Muscle, Smooth / physiology
        • Oxidation-Reduction / drug effects
        • Patch-Clamp Techniques
        • Potassium Channels / drug effects
        • Potassium Channels / physiology
        • Sulfhydryl Compounds / pharmacology

        Grant Funding

        • 1 F32HL09294 / NHLBI NIH HHS
        • HL41084 / NHLBI NIH HHS

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