Chan KW et al. (1996), Control of channel activity through a unique am...

XB-ART-17400

Proc Natl Acad Sci U S A 1996 Nov 26;9324:14193-8. doi: 10.1073/pnas.93.24.14193.

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Control of channel activity through a unique amino acid residue of a G protein-gated inwardly rectifying K+ channel subunit.

Chan KW , Sui JL , Vivaudou M , Logothetis DE .

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G protein-gated inwardly rectifying K+ (GIRK) channels, which are important regulators of membrane excitability both in heart and brain, appear to function as heteromultimers. GIRK1 is unique in the GIRK channel family in that although it is by itself inactive, it can associate with the other family members (GIRK2-GIRK5) to enhance their activity and alter their single-channel characteristics. By generating a series of chimeras, we identified a phenylalanine residue, F137, in the pore region of GIRK1 that critically controls channel activity. F137 is found only in GIRK1, while the remaining GIRK channels possess a conserved serine residue in the analogous position. The single-point mutant GIRK4(S143F) behaved as a GIRK1 analog, forming multimers with GIRK2, GIRK4, or GIRK5 channels that exhibited prolonged single-channel open-time duration and enhanced activity compared with that of homomultimers. Expression of the corresponding GIRK1 (F137S) mutant alone resulted in appreciable channel activity with novel characteristics that was further enhanced upon coexpression with other GIRK subunits. Thus, although the F137 residue renders the GIRK1 subunit inactive, when combined with other GIRK heteromeric partners it alters their gating and contributes to their enhanced activity.

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Species referenced: Xenopus
Genes referenced: kcnj3 kcnj5 kcnj6

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