G 蛋白による神経型電位依存性 Ca<sup>2＋</sup>チャネルの制御機構

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  • Binding of Gα<sub>o</sub> <i>N</i>-Terminus is Responsible for the Voltage-Resistant Inhibition of α<sub>1A</sub> (P/Q-Type, Ca<sub>v</sub>2.1) Ca<sup>2+</sup> Channels
  • G蛋白による神経型電位依存性Ca〔2+〕チャネルの制御機構
  • G タンパク ニ ヨル シンケイガタ デンイ イゾンセイ Ca 2 チャネル ノ セイギョ キコウ

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G-protein-mediated inhibition of presynaptic voltage-dependent Ca2+ channels is comprised of voltage-dependent and -resistant components. The former is caused by a direct interaction of Ca2+ channel α1 subunits with Gβγ, whereas the latter has not been well characterized. Here, we show that the N-terminus of Gαo is critical for the interaction with the C-terminus of the P/Q-type channel subunit, and that the binding induces voltage-resistant inhibition. A P/Q-type C-terminal peptide, an antiserum raised against the Gαo N-terminus, and a Gαo N-terminal peptide all attenuated the voltage-resistant inhibition of P/Q-type currents. Furthermore, the N-terminus of Gαo bound to the C-terminus of α1A in vitro, which was prevented either by the P/Q-type channel C-terminal or Gαo N-terminal peptide. Although the C-terminal domain of the N-type channel showed similar ability to binding with Gαo N-terminus, the above-mentioned treatments were ineffective in the N-type channel current. These findings demonstrate that the voltage-resistant inhibition of the P/Q-type channel is caused by the interaction between the C-terminal domain of the Ca2+ channel α1A subunit and the N-terminal region of Gαo.<br>

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  • 薬学雑誌

    薬学雑誌 122 (8), 565-572, 2002-08-01

    公益社団法人 日本薬学会

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