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Letters to Nature

Nature 425, 531-535 (2 October 2003) | doi:10.1038/nature02003; Received 11 June 2003; Accepted 26 August 2003

Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels

Xiang Dong Tang1, Rong Xu1, Mark F. Reynolds2, Maria L. Garcia3, Stefan H. Heinemann4 & Toshinori Hoshi1

  1. Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
  2. Department of Chemistry, Saint Joseph's University, 5600 City Avenue, Philadelphia, Pennsylvania 19131, USA
  3. Department of Ion Channels, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey 07065, USA
  4. Research Unit Molecular and Cellular Biophysics, Medical Faculty of the Friedrich Schiller University Jena, Drackendorfer Strasse 1, D-07747 Jena, Germany

Correspondence to: Toshinori Hoshi1 Email: hoshi@hoshi.org

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Haem is essential for living organisms, functioning as a crucial element in the redox-sensitive reaction centre in haemproteins1. During the biogenesis of these proteins, the haem cofactor is typically incorporated enzymatically into the haem pockets of the apo-haemprotein as the functionally indispensable prosthetic group2, 3. A class of ion channel, the large-conductance calcium-dependent Slo1 BK channels, possesses a conserved haem-binding sequence motif. Here we present electrophysiological and structural evidence showing that haem directly regulates cloned human Slo1 channels and wild-type BK channels in rat brain. Both oxidized and reduced haem binds to the hSlo1 channel protein and profoundly inhibits transmembrane K+ currents by decreasing the frequency of channel opening. This direct regulation of the BK channel identifies a previously unknown role of haem as an acute signalling molecule.