Zn2+ activates large conductance Ca2+-activated K+ channel via an intracellular domain

Shangwei Hou, Leif E. Vigeland, Guangping Zhang, Rong Xu, Min Li, Stefan H. Heinemann, Toshinori Hoshi

Research output: Contribution to journalArticle

Abstract

Zinc is an essential trace element and plays crucial roles in normal development, often as an integral structural component of transcription factors and enzymes. Recent evidence suggests that intracellular Zn2+ functions as a signaling molecule, mediating a variety of important physiological phenomena. However, the immediate effectors of intracellular Zn2+ signaling are not well known. We show here that intracellular Zn2+ potently and reversibly activates large-conductance voltage- and Ca2+-activated Slo1 K+ (BK) channels. The full effect of Zn2+ requires His365 in the RCK1 (regulator of conductance for K+) domain of the channel. Furthermore, mutation of two nearby acidic residues, Asp367 and Glu399, also reduced activation of the channel by Zn2+, suggesting a possible structural arrangement for Zn2+ binding by the aforementioned residues. Extracellular Zn2+ activated Slo1 BK channels when coexpressed with Zn2+-permeable TRPM7 (transient receptor potential melastatin 7) channels. The results thus demonstrate that Slo1 BK channels represent a positive and direct effector of Zn2+ signaling and may participate in sculpting cellular response to an increase in intracellular Zn2+ concentration.

Original languageEnglish (US)
Pages (from-to)6434-6442
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number9
DOIs
StatePublished - Feb 26 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Zn<sup>2+</sup> activates large conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channel via an intracellular domain'. Together they form a unique fingerprint.

  • Cite this

    Hou, S., Vigeland, L. E., Zhang, G., Xu, R., Li, M., Heinemann, S. H., & Hoshi, T. (2010). Zn2+ activates large conductance Ca2+-activated K+ channel via an intracellular domain. Journal of Biological Chemistry, 285(9), 6434-6442. https://doi.org/10.1074/jbc.M109.069211