G-protein-coupled inwardly rectifying potassium channel

HTxR, serotonin receptor CB1R, cannabinoid-1 DAT, dopamine transporter GABA, y-aminobutyric acid Kir3 channels, G protein-coupled inwardly rectifying potassium channels LSD, lysergic acid diethylamide i -OR, H-opioid receptor nAChR, nicotinic acetylcholine receptor NET, norepinephrine transporter NMDAR, N -methyl-D-aspartate receptor SERT, serotonin transporter VMAT, vesicular monoamine transporter indicates data not available. 

D2-like receptors couple mainly to Gi/o proteins, as mentioned above. However, there is no direct evidence to support this coupling for the release-modulating autoreceptors. Moreover, the subsequent intracellular signal transduction has never been studied directly in axon terminals. Mouse AtT-20 pituitary cells, which release acetylcholine and adrenocorticotropic hormone, have been used as a model for axon terminals. When expressed in these cells, D3 receptors mediated inhibition of P/Q-type calcium channels and activation of G protein-coupled inward rectifier potassium channels (Kuzhikandathil et al. 1998 Kuzhikandathil and Oxford 1999). Both would explain the autoreceptor-mediated inhibition of dopamine exocytosis. 

Lovinger DM, Merritt A, Reyes D (1994) Involvement of N- and non-N-type calcium channels in synaptic transmission at corticostriatal synapses. Neurosci 62(1) 31 10 McAllister SD, Griffin G, Satin LS, Abood ME (1999) Cannabinoid receptors can activate and inhibit G protein-coupled inwardly rectifying potassium channels in a xenopus oocyte expression system. J Pharmacol Exp Ther 291(2) 618-26... 

Gregerson KA, Flagg TP, O Neill TJ, Anderson M, Lauring O, Horel JS, Welling PA (2001) Identification of G protein-coupled, inward rectifier potassium channel gene products from the rat anterior pituitary gland. Endocrinology 742 2820—2832. 

Fig. 1. P -AR subtype-specific signaling in cardiac myocytes. Cav, caveolae GIRK, G protein coupled inwardly rectifying potassium channel If, nonselective cation channel NHERF, indicates NHERF/EBP50 (Na+/H+ exchange regulatory factor) or arelated protein PLB, phospholamban PSD-95, indicates PSD-95 or a related protein TnC, troponin C TnT, troponin T. Dashed lines indicate postulated signaling pathways that have not been verified experimentally.

Guo J, Ikeda SR (2004) Endocannabinoids modulate N-type calcium channels and G-protein-coupled inwardly rectifying potassium channels via CB 1 cannabinoid receptors heterologously expressed in mammalian neurons. Mol Pharmacol 65 665-674... 

Leaney, J. L. and Tinker, A. (2000) The role of members of the pertussis toxin-sensitive family of G proteins in coupling receptors to the activation of the G protein-gated inwardly rectifying potassium channel. Proc. Natl. Acad. Sci. USA 97, 5651-5656. 

Receptor tolerance occurs at the level of the opioid receptor and involves receptor desensitization upon chronic or repeated exposure to opioids. The concept of receptor desensitization underlies acute-onset opioid tolerance. Receptor desensitization means loss in the coupling of mu opioid receptor to its cellular effectors, particularly its major cellular effector - the G-protein-regulated inwardly rectifying potassium channel. Several potential mechanisms could account for tolerance at this level of organization, but changes in coupling to G protein and perhaps expression of the receptors on the cell surface appear to be most important. 

Yamakura, T., Lewohl, J. M. Harris, R. A. Differential effects of general anesthetics on G protein-coupled inwardly rectifying and other potassium channels, Anesthesiology 2001, 95, 144-153. 

Ion channels. G proteins are also involved in the coupling of some receptors to ion channels. A classic example is the modulation of inwardly rectifying potassium channels by m2 acetylcholine receptors. Other receptors have been shown to modulate Ca and/or K channels by either G protein a or Py subunits. 

Kubo Y, Murata Y (2001) Control of rectification and permeation by two distinct sites after the second transmembrane region in Kir2.1 K+ channel. J Physiol 531 645-660 Kubo Y, Baldwin TJ, Jan YN, Jan LY (1993a) Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature (Lond) 362 127-133 Kubo Y, Reuveny E, Slesinger PA, Jan YN, Jan LY (1993b) Primary structure and functioned expression of a rat G-protein-coupled muscarinic potassium channel. Nature (Lond) 364 802-806... 

---