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Enzymatic activation of voltage-gated potassium channels

Naturevolume 442pages696699 (2006) | Download Citation



Voltage-gated ion channels in excitable nerve, muscle, and endocrine cells generate electric signals in the form of action potentials1. However, they are also present in non-excitable eukaryotic cells and prokaryotes, which raises the question of whether voltage-gated channels might be activated by means other than changing the voltage difference between the solutions separated by the plasma membrane. The search for so-called voltage-gated channel activators is motivated in part by the growing importance of such agents in clinical pharmacology. Here we report the apparent activation of voltage-gated K+ (Kv) channels by a sphingomyelinase.

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We thank K. Lynch (University of Virginia) for sharing the cDNA clone of Lr2 isoform of SMase D; R. Joho and K. Swartz for Kv2.1 cDNA; G. Robertson and B. Ganetzky for mEAG cDNA; L. Salkoff and F. Horrigan for mSlo cDNA; K. Swartz for Shaker-IR cDNA in the pGEM-HESS vector and the HaTx sample; C.-X. Yuan for LC–MS/MS sequencing; J. R. Martinez-Francois for chemical structure drawing; R. MacKinnon for comments; and P. De Weer for review and discussion of our manuscript. This study was supported by a grant from the National Institute of General Medical Sciences to Z.L.

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  1. Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Pennsylvania, 19104, Philadelphia, USA

    • Yajamana Ramu
    • , Yanping Xu
    •  & Zhe Lu


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Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding author

Correspondence to Zhe Lu.

Supplementary information

  1. Supplementary Figure 1

    LCMS/MS-identified peptide sequences match those of Lr1 and Lr2 isoforms of SMase D. (JPG 62 kb)

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