TY - JOUR T1 - Gβγ and K<sub>ACh</sub>: Old Story, New Insights JF - Science's STKE JO - Sci. STKE SP - pe32 LP - pe32 DO - 10.1126/stke.2003.194.pe32 VL - 2003 IS - 194 AU - Mirshahi, Tooraj AU - Jin, Taihao AU - Logothetis, Diomedes E. Y1 - 2003/08/05 UR - http://stke.sciencemag.org/content/2003/194/pe32.abstract N2 - Dissociation of the heterotrimeric GTP-binding protein (G protein) βγ subunits from the α subunit is a prerequisite step in the ability of these proteins to signal to downstream effectors. There is evidence that ions such as Na+ and Cl- can facilitate this dissociation. Interestingly, for KACh, the first known effector for Gβγ, intracellular Na+ can also activate the channel independently of Gβγ. Both Gβγ and Na+ strengthen channel interactions with the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), an event thought to be essential in opening the channel. PIP2 interacts with channel regions that form a binding pocket proximal to the transmembrane domains and is likely to exert a tangential, pulling force to mechanically open a gate at the cytoplasmic face of the channel pore. The tangential force generated by channel-PIP2 interactions is the likely force behind gating in all inwardly rectifying K+ channels. The gate opens when the lower part of the pore-lining transmembrane α helix pivots around a glycine residue in the middle of the helix. This mechanism of channel gating is conserved among K+ channels from bacteria to mammals and may represent a common mechanism for K+ channel gating. ER -