Send to

Choose Destination
Cell. 1995 Nov 3;83(3):443-9.

Identification of domains conferring G protein regulation on inward rectifier potassium channels.

Author information

Department of Molecular and Cellular Biology Harvard University Cambridge, Massachusetts 02138, USA.


Cardiac m2 muscarinic acetylcholine receptors reduce heart rate by coupling to heterotrimeric (alpha beta gamma) guanine nucleotide-binding (G) proteins that activate IKACh, an inward rectifier K+ channel (IRK). Activation of the GIRK subunit of IKACh requires G beta gamma subunits; however, the structural basis of channel regulation is unknown. To determine which sequences confer G beta gamma regulation upon IRKs, we generated chimeric proteins composed of GIRK and RB-IRK2, a related, G protein-insensitive channel. Importantly, a chimeric channel containing the hydrophobic pore region of RB-IRK2 joined to the amino and carboxyl termini of GIRK exhibited voltage- and receptor-dependent activation in Xenopus oocytes. Furthermore, carboxy-terminal sequences specific to this chimera and GIRK bound G beta gamma subunits in vitro. Thus, G beta gamma may regulate IRKs by interacting with sequences adjacent to the putative channel pore.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center