Related Experiment Video
Updated: Aug 18, 2026

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
Published on: May 18, 2009
Synergistic activation of G protein-gated inwardly rectifying potassium channels by cholesterol and PI(4,5)P2
Anna N Bukiya1, Avia Rosenhouse-Dantsker2
1Department of Pharmacology, The University of Tennessee HSC, Memphis, TN 38163, United States.
Abstract:
G-protein gated inwardly rectifying potassium (GIRK or Kir3) channels play a major role in the control of the heart rate, and require the membrane phospholipid phosphatidylinositol-bis-phosphate (PI(4,5)P2) for activation. Recently, we have shown that the activity of the heterotetrameric Kir3.1/Kir3.4 channel that underlies atrial KACh currents was enhanced by cholesterol. Similarly, the activities of both the Kir3.4 homomer and its active pore mutant Kir3.4* (Kir3.4_S143T) were also enhanced by cholesterol. Here we employ planar lipid bilayers to investigate the crosstalk between PI(4,5)P2 and cholesterol, and demonstrate that these two lipids act synergistically to activate Kir3.4* currents. Further studies using the Xenopus oocytes heterologous expression system suggest that PI(4,5)P2 and cholesterol act via distinct binding sites. Whereas PI(4,5)P2 binds to the cytosolic domain of the channel, the putative binding region of cholesterol is located at the center of the transmembrane domain overlapping the central glycine hinge region of the channel. Together, our data suggest that changes in the levels of two key membrane lipids - cholesterol and PI(4,5)P2 - could act in concert to provide fine-tuning of Kir3 channel function.
Related Concept Videos
Amplifying Signals via Second Messengers
Activation and Inactivation of G Proteins
G-Protein Gated Ion Channels
Sensory organs,...
GPCRs Regulate Adenylyl Cylase Activity
Two...
IP3/DAG Signaling Pathway
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...

