Editors' ChoiceChannels

Of Hemin Bondage

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Science's STKE  07 Oct 2003:
Vol. 2003, Issue 203, pp. tw388-TW388
DOI: 10.1126/stke.2003.203.tw388

Tang et al. used structural and electrophysiological analysis to uncover a novel role for heme (the iron-containing cofactor that forms a prosthetic group essential for oxygen transport in heme-containing proteins) as an inhibitor of K+ flux through Slo1 BK ion channels. Slo1 channels are a class of Ca2+-activated K+ channels that provide a hyperpolarizing brake on Ca2+-mediated excitotoxicity. Noting that these channels contain a conserved heme-binding motif, the authors expressed human Slo1 (hSlo1) channels in HEK tsA cells and recorded currents from excised inside-out membrane patches. Application of hemin (the Fe3+ oxidation product of heme) to the intracellular side of Slo1 channels inhibited K+ current with a Kd comparable to that of heme association with known heme-binding proteins (45 to 120 nM). Heme's effect did not depend on iron oxidative state; however, neither heme incorporated into a peptide nor the iron-free heme precursor protoporphyrin IX were active. K+ current through native BK channels in patches from rat hippocampal neurons was also heme-sensitive. Electron paramagnetic resonance analysis of hemin association with a peptide containing the putative heme-binding segment (CKACH) suggested that hSlo1 bound heme in a manner similar to that of the cytochromes. Because heme is released from heme proteins in response to injury, hypoxia, and stress, the authors propose that heme modulation of BK channel function may be physiologically relevant.

X. D. Tang, R. Xu, M. F. Reynolds, M. L. Garcia, S. H. Heinemann, T. Hoshi, Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels. Nature 425, 531-535 (2003). [Online Journal]

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