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


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.

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Figure 1: Haemin inhibits the opening of Slo1 channels.
Figure 2: Physiological relevance of haem inhibition.
Figure 3: Haemin binding to hSlo-HBP23.
Figure 4: Mutations in the CKACH segment disrupt the haemin sensitivity of the hSlo1 channel.


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We thank L. Ciali for critically reading the manuscript; V. Avdonin and R. Wassef for help with constructing the mutants; and P. Angiolillo for use of the EPR spectrometer. This work was supported, in part, by the NIH and the American Heart Association.

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Correspondence to Toshinori Hoshi.

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M. L. Garcia is an employee of Merck & Co. Inc. and potentially owns stock and/or holds stock options in the company.

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Tang, X., Xu, R., Reynolds, M. et al. Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels. Nature 425, 531–535 (2003).

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