Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels.
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Tang XD, Xu R, Reynolds MF, Garcia ML, Heinemann SH, Hoshi T
Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels.
Nature. 2003 Oct 2;425(6957):531-5.
- PubMed ID
- 14523450 [ View in PubMed]
- Abstract
Haem is essential for living organisms, functioning as a crucial element in the redox-sensitive reaction centre in haemproteins. 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 group. 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.