Structural basis of inward rectification:: Cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 Å resolution

Inward rectifier K+ channels govern the resting membrane voltage in many cells. Regulation of these ion channels via G protein-coupled receptor signaling underlies the control of heart rate and the actions of neurotransmitters in the central nervous system. We have determined the protein structure formed by the intracellular N- and C termini of the G protein-gated inward rectifier K+ channel GIRK1 at 1.8 Angstrom resolution. A cytoplasmic pore, conserved among inward rectifier K+ channels, extends the ion pathway to 60 Angstrom, nearly twice the length of a canonical transmembrane K+ channel. The cytoplasmic pore is lined by acidic and hydrophobic amino acids, creating a favorable environment for polyamines, which block the pore. These results explain in structural and chemical terms the basis of inward rectification, and they also have implications for G protein regulation of GIRK channels.