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Redox-sensitive extracellular gates formed by auxiliary β subunits of calcium-activated potassium channels

Nature Structural & Molecular Biology volume 10, pages 448–454 (2003)Cite this article

Abstract

An important step to understanding ion channels is identifying the structural components that act as the gates to ion movement. Here we describe a new channel gating mechanism, produced by the β3 auxiliary subunits of Ca2+-activated, large-conductance BK-type K+ channels when expressed with their pore-forming α subunits. BK β subunits have a cysteine-rich extracellular segment connecting two transmembrane segments, with small cytosolic N and C termini. The extracellular segments of the β3 subunits form gates to block ion permeation, providing a mechanism by which current can be rapidly diminished upon cellular repolarization. Furthermore, this gating mechanism is abolished by reduction of extracellular disulfide linkages, suggesting that endogenous mechanisms may regulate this gating behavior. The results indicate that auxiliary β subunits of BK channels reside sufficiently close to the ion permeation pathway defined by the α subunits to influence or block access of small molecules to the permeation pathway.

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Figure 1: Auxiliary β subunits have different effects on instantaneous current-voltage properties of BK currents.
Figure 2: The extracellular loop of the BK β3 auxiliary subunit produces outward rectification in BK currents.
Figure 3: Extracellular application of DTT abolishes rectification and alters sensitivity to CTX.
Figure 4: Outward rectification arises from a rapid voltage-dependent, DTT-sensitive block of single channels.
Figure 5: The extracellular blocking mechanism requires the contributions of more than one β3 subunit.
Figure 6: Diagrams showing various stoichiometric combinations of α + β3 subunits.

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Acknowledgements

We thank the Department of Anesthesiology, Washington University School of Medicine for material support. X.Z. was supported by an AHA-Missouri affiliate fellowship.

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  1. Department of Anesthesiology, Washington University School of Medicine, Box 8054, St. Louis, 63110, Missouri, USA

    Xu-Hui Zeng, Xiao-Ming Xia & Christopher J Lingle

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Correspondence to Christopher J Lingle.

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Zeng, XH., Xia, XM. & Lingle, C. Redox-sensitive extracellular gates formed by auxiliary β subunits of calcium-activated potassium channels. Nat Struct Mol Biol 10, 448–454 (2003). https://doi.org/10.1038/nsb932

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