The GIRK 1 subunit potentiates G protein activation of cardiac GIRK 1 / 4 hetero - tetramers 6

Abstract

11 G protein gated inward rectifier potassium (GIRK) channels are gated by direct binding of G 12 protein beta-gamma subunits (Gβγ), signaling lipids, and intracellular Na +. In cardiac 13 pacemaker cells, hetero-tetramer GIRK1/4 channels and homo-tetramer GIRK4 channels play 14 a central role in parasympathetic slowing of heart rate. It is known that the Na + binding site of 15 the GIRK1 subunit is defective, but the functional difference between GIRK1/4 hetero-16 tetramers and GIRK4 homo-tetramers remains unclear. Here, using purified proteins and the 17 lipid bilayer system, we characterize Gβγ and Na + regulation of GIRK1/4 hetero-tetramers and 18 GIRK4 homo-tetramers. We find in GIRK4 homo-tetramers that Na + binding increases Gβγ 19 affinity and thereby increases the GIRK4 responsiveness to G protein stimulation. GIRK1/4 20 hetero-tetramers are not activated by Na + , but rather are in a permanent state of high 21 responsiveness to Gβγ, suggesting that the GIRK1 subunit functions like a GIRK4 subunit with 22

Cite this paper

@inproceedings{Touhara2016TheG1, title={The GIRK 1 subunit potentiates G protein activation of cardiac GIRK 1 / 4 hetero - tetramers 6}, author={Kouki K. Touhara and Weiwei Wang}, year={2016} }