TY - JOUR T1 - Interaction of Gα<sub>q</sub> and Kir3, G Protein-Coupled Inwardly Rectifying Potassium Channels JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1179 LP - 1184 DO - 10.1124/mol.106.032508 VL - 71 IS - 4 AU - Takeharu Kawano AU - Peng Zhao AU - Christina V. Floreani AU - Yasuko Nakajima AU - Tohru Kozasa AU - Shigehiro Nakajima Y1 - 2007/04/01 UR - http://molpharm.aspetjournals.org/content/71/4/1179.abstract N2 - Activation of substance P receptors, which are coupled to Gαq, inhibits the Kir3.1/3.2 channels, resulting in neuronal excitation. We have shown previously that this channel inactivation is not caused by reduction of the phosphatidylinositol 4,5-bisphosphate level in membrane. Moreover, Gαq immunoprecipitates with Kir3.2 (J Physiol564:489–500, 2005), suggesting that Gαq interacts with Kir3.2. Positive immunoprecipitation, however, does not necessarily indicate direct interaction between the two proteins. Here, the glutathione transferase pull-down assay was used to investigate interaction between Gαq and the K+ channels. We found that Gαq interacted with N termini of Kir3.1, Kir3.2, and Kir3.4. However, Gαq did not interact with the C terminus of any Kir3 or with the C or N terminus of Kir2.1. TRPC6 is regulated by the signal initiated by Gαq. Immunoprecipitation, however, showed that Gαq did not interact with TRPC6. Thus, the interaction between Gαq and the Kir3 N terminus is quite specific. This interaction occurred in the presence of GDP or GDP-AlF–4. The Gαq binding could take place somewhere between residues 51 to 90 of Kir3.2; perhaps the segment between 81 to 90 residues is crucial. Gβγ, which is known to bind to N terminus of Kir3, did not compete with Gαq for the binding, suggesting that these two binding regions are different. These findings agree with the hypothesis (J Physiol564:489–500, 2005) that the signal to inactivate the Kir3 channel could be mainly transmitted directly from Gαq to Kir3. The American Society for Pharmacology and Experimental Therapeutics ER -