The unusual stoichiometry of ADP activation of the KATP channel.

Eric Hosy, Michel Vivaudou
Front. Physiol.. 2014-01-01; 5:
DOI: 10.3389/fphys.2014.00011

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1. Front Physiol. 2014 Jan 28;5:11. doi: 10.3389/fphys.2014.00011. eCollection 2014.

The unusual stoichiometry of ADP activation of the KATP channel.

Hosy E(1), Vivaudou M(1).

Author information:
(1)Institut de Biologie Structurale, University Grenoble Alpes Grenoble, France ;
Laboratory of Excellence, Ion Channel Science and Therapeutics, CNRS, Institut de
Biologie Structurale Grenoble, France ; CEA, DSV, Institut de Biologie
Structurale Grenoble, France.

KATP channels, oligomers of 4 pore-forming Kir6.2 proteins and 4 sulfonylurea
receptors (SUR), sense metabolism by monitoring both cytosolic ATP, which closes
the channel by interacting with Kir6.2, and ADP, which opens it via SUR. SUR
mutations that alter activation by ADP are a major cause of KATP channelopathies.
We examined the mechanism of ADP activation by analysis of single-channel and
macropatch recordings from Xenopus oocytes expressing various mixtures of
wild-type SUR2A and an ADP-activation-defective mutant. Evaluation of the data by
a binomial distribution model suggests that wild-type and mutant SURs freely
co-assemble and that channel activation results from interaction of ADP with only
2 of 4 SURs. This finding explains the heterozygous nature of most KATP
channelopathies linked to mutations altering ADP activation. It also suggests
that the channel deviates from circular symmetry and could function as a

DOI: 10.3389/fphys.2014.00011
PMCID: PMC3904077
PMID: 24478723

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