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PubMed 21982822


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir3.2



Title: INTERACTIONS OF CATIONS WITH THE CYTOPLASMIC PORES OF INWARD RECTIFIER K+ CHANNELS IN THE CLOSED STATE.

Authors: Atsushi Inanobe, Atsushi Nakagawa, Yoshihisa Kurachi

Journal, date & volume: , 2011 Oct 9 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21982822


Abstract
Ion channels gate at membrane-embedded domains by changing their conformation along the ion conduction pathway. Inward rectifier K(+) (Kir) channels possess a unique extramembrane cytoplasmic domain that extends this pathway. However, the relevance and contribution of this domain to ion permeation remain unclear. By qualitative x-ray crystallographic analysis, we found that the pore in the cytoplasmic domain of Kir3.2 binds cations in a valency-dependent manner and does not allow the displacement of Mg(2+) by monovalent cations or spermine. Electrophysiological analyses revealed that the cytoplasmic pore of Kir3.2 selectively binds positively charged molecules and has a higher affinity for Mg(2+) when it has a low probability of being open. The selective blocking of chemical modification of the side chain of pore-facing residues by Mg(2+) indicates that the mode of binding of Mg(2+) is likely to be similar to that observed in the crystal structure. These results indicate that the Kir3.2 crystal structure has a closed conformation with a negative electrostatic field potential at the cytoplasmic pore, the potential of which may be controlled by conformational changes in the cytoplasmic domain to regulate ion diffusion along the pore.