Identification of structural elements involved in G protein gating of the GIRK1 potassium channel.

Chimeras of GIRK1 and IRK1, a G protein-insensitive inward rectifier, are activated by coexpression of G beta gamma if they contain either the N-terminal or part of the C-terminal hydrophilic domain of GIRK1. The N-terminal domain of GIRK1 also facilitates the fast rates of activation and deactivation following m2 muscarinic receptor stimulation. The hydrophobic core of GIRK1 (M1-H5-M2) is important for determining the brief single-channel open times typical of GIRK1 but not important for determining G beta gamma sensitivity. Coexpression with CIR revealed that the gating properties associated with different GIRK1 domains could not have arisen from altered ability to form heteromultimers. These results implicate specific regions of GIRK1 in G protein activation and suggest that GIRK1 may be closely linked to the m2 muscarinic receptor-G protein complex.