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

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.

journal_name

Nature

journal_title

Nature

authors

Tang XD,Xu R,Reynolds MF,Garcia ML,Heinemann SH,Hoshi T

doi

10.1038/nature02003

keywords:

subject

Has Abstract

pub_date

2003-10-02 00:00:00

pages

531-5

issue

6957

eissn

0028-0836

issn

1476-4687

pii

nature02003

journal_volume

425

pub_type

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