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Ion Channels and Excitable Membranes

開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Activation efficiency of the G protein gated inwardly rectifying potassium channel depends on distance from the Gq but not Gi/o coupled receptors

  • P1-005
  • 立山 充博 / Michihiro Tateyama:1,2 久保 義弘 / YOSHIHIRO KUBO:1,2 
  • 1:生理学研究所・分子生理・神経機能素子 / Div Biophys and Neurobiol, Dept Physiol Sci, NIPS, Aichi, Japan 2:総研大院生命科学生理 / Dept Physiol Sci, SOKENDAI, Kanagawa, Japan 

The G protein gated inwardly rectifying potassium (GIRK) channel negatively modulates the neuronal excitability upon the activation of G protein coupled receptors. Activity of the GIRK channel is regulated by Gβγ subunits released mostly from Pertussis toxin (PTX) sensitive Gαi/o subunits. On the other hand, it has been reported that the Gβγ released from PTX resistant Gα subunits also activates the GIRK channel, when the expression level of the coupling receptors is high. With a high surface density of receptors, number of receptors adjacent to the GIRK channel is expected to increase efficiency of the GIRK channel activation. Here we examined this possibility, by linking the receptor with the channel by using various lengths of glycine rich linkers. A Gq coupled muscarinic receptor type1 (M1R) evoked the GIRK current upon the application of the agonist when the number of the amino acid residues of the linker was 100 or less, whereas it failed when the number was 268 or more. The M1R-induced GIRK current remained after the treatment with PTX, suggesting that the Gβγ subunits released from Gαq subunit activated the GIRK channel when the M1R located adjacent to the channel. In contrast to the M1R, a Gi/o coupled muscarinic receptor type 2 (M2R) activated the GIRK channel when the linker size was nearly 541 amino acid residues. From these results, it was suggested that the activation efficiency of the GIRK channel depends on the distance from the Gq-coupled M1R but not from the Gi/o-coupled M2R.

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