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Redox-dependent Cd2+ inhibition of BK-type Ca2+-activated K+ channels.
Large-conductance Ca2+-activated K+ channels (BK channels) are formed by Slo1 subunits as a homotetramer. Besides Ca2+, other divalent cations, such as Cd2+, also activate BK channels when applied intracellularly by shifting the conductance-voltage relation to more negative voltages. However, we found that if the inside-out patch containing BK channels was treated with solution containing reducing agents such as dithiothreitol (DTT), then subsequent Cd2+ application completely inhibited BK currents. The DTT-dependent Cd2+ inhibition could be reversed by treating the patch with solutions containing H2O2, suggesting that a redox reaction regulates the Cd2+ inhibition of BK channels. Similar DTT-dependent Cd2+ inhibition was also observed in a mutant BK channel, Core-MT, in which the cytosolic domain of the channel is deleted, and in the proton-activated Slo3 channels but not observed in the voltage-gated Shaker K+ channels. A possible mechanism for the DTT-dependent Cd2+ inhibition is that DTT treatment breaks one or more disulfide bonds between cysteine pairs in the BK channel protein and the freed thiol groups coordinate with Cd2+ to form an ion bridge that blocks the channel or locks the channel at the closed state. However, surprisingly, none of the mutations of all cysteine residues in Slo1 affect the DTT-dependent Cd2+ inhibition. These results are puzzling, with an apparent contradiction: on one hand, a redox reaction seems to regulate Cd2+ inhibition of the channel, but on the other hand, no cysteine residue in the Slo1 subunit seems to be involved in such inhibition.
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Related Subject Headings
- Oxidation-Reduction
- Large-Conductance Calcium-Activated Potassium Channels
- Humans
- Dithiothreitol
- Cadmium
- Biophysics
- Animals
- 51 Physical sciences
- 34 Chemical sciences
- 31 Biological sciences
Citation
![Journal cover image](https://secure.syndetics.com/index.aspx?isbn=/lc.gif&issn=1542-0086&client=dukeuniv)
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Oxidation-Reduction
- Large-Conductance Calcium-Activated Potassium Channels
- Humans
- Dithiothreitol
- Cadmium
- Biophysics
- Animals
- 51 Physical sciences
- 34 Chemical sciences
- 31 Biological sciences