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SLO-2, a K+ channel with an unusual Cl− dependence

Nature Neuroscience volume 3, pages 771–779 (2000)Cite this article

Abstract

The gating of different potassium channels depends on many diverse factors. We now report a unique example of a K+ channel with a Cl− dependence. The slo-2 gene was cloned from Caenorhabditis elegans and is widely expressed in both neurons and muscles; it was highly abundant, as suggested by its high representation in the C. elegans EST database. SLO-2, like its paralogue, SLO-1, was also dependent on Ca2+. We show by site-directed mutagenesis that its requirements for both Cl− and Ca2+ are synergistic and associated with the same functional domain. SLO-2's dependence on Cl− implies that intracellular Cl− homeostasis may be important in regulating cellular excitability through this unusual K+ channel.

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Figure 1: Tissue-specific expression pattern of slo-2.
Figure 2: The SLO family of K+ channels consists of three known members gated by voltage and modulated by Ca2+ (SLO-1), Cl− and Ca2+ (SLO-2) or pH (SLO-3).
Figure 3: SLO-2 requires both intracellular Cl− and Ca2+ for activation.
Figure 4: Increasing Cl− or Ca2+ increases SLO-2 activity.
Figure 5: SLO-2 is activated by depolarization, as shown by the representative traces of a single inside-out patch under progressively higher voltages.
Figure 6: SLO-2 is also activated by I−.
Figure 7: Mutations in the chloride bowl of SLO-2 produced channels with decreased sensitivity to Cl− and Ca2+.
Figure 8: The neu and neg mutants are poorly activated by Cl− and Ca2+.

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Acknowledgements

We thank K. Magelby and C. Nimigean for comments and suggestions and members of the Salkoff lab and M. Nonet lab for technical help and suggestions. Support from NIH to L.S. and NIH GM07200 to A.Y.

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid, Saint Louis, 63110, Missouri, USA

    Alex Yuan, Alice Butler, Nina Walton, Aguan Wei & Lawrence Salkoff

  2. Division of Oral Biology, Box 0152, University of California, San Francisco, 94143, California, USA

    Michelle Dourado

  3. Department of Genetics, Washington University School of Medicine, 660 South Euclid, Saint Louis, 63110, Missouri, USA

    Lawrence Salkoff

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Correspondence to Lawrence Salkoff.

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Yuan, A., Dourado, M., Butler, A. et al. SLO-2, a K+ channel with an unusual Cl− dependence. Nat Neurosci 3, 771–779 (2000). https://doi.org/10.1038/77670

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