G protein-activated inward rectifying K+channel

Kd 50 nM for GIRK [G-protein-activated inwardly rectifying K+ channel] activation) and persistent in the absence of competing Ga-GDP, Py-effector binding is not irreversible. 

Bunemann, M., Bucheler, M. M., Philipp, M., Lohse, M. J., and Hein, L. (2001). Activation and deactivation kinetics of alpha(2A)- and alpha(2C)-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents. / Biol. Chem. 276, 47512-47517. 

Kofuji, R, Davidson, N. and Lester, H. Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G protein Py subunits and function as... 

Filippov AK, Femandez-Femandez JM, Marsh SJ et al (2004) Activation and inhibition of neuronal G protein-gated inwardly rectifying K(+) channels by P2Y nucleotide receptors. Mol Pharmacol 66 468-77... 

Loyet KM, Kowalchyk JA, Chaudhary A et al (1998) Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-dependent activator protein for secretion (CAPS), a potential phos-phoinositide effector protein for regulated exocytosis. J Biol Chem 273 8337 13 Luscher C, Jan LY, Stoffel M et al (1997) G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron 19 687-95... 

Feuerstein TJ, Hertting G, Jackisch R (1985) Modulation of hippocampal serotonin (5-HT) release by endogenous adenosine. Eur J Pharmacol 107 233 42 Filippov AK, Simon J, Barnard EA et al (2003) Coupling of the nucleotide P2Y4 receptor to neuronal ion channels. Br J Pharmacol 138 400-6 Filippov AK, Fernandez-Femandez JM, Marsh SJ et al (2004) Activation and inhibition of neuronal G protein-gated inwardly rectifying K+ channels by P2Y nucleotide receptors. Mol Pharmacol 66 468-77... 

The role of Gpy, released from pertussis toxin-sensitive G proteins, in coupling activated receptor to effectors further complicates specificity. Delta opioids activate G protein-coupled inwardly rectifying K+ channels [50] activation of such channels occurs by direct binding of Gp-y to various regions of the channel [51]. Delta agonist-mediated increase in the release of Ca2+ from intracellular stores in NG108-15 cells is mediated by Gp-y subunits [52], and Gp antibodies inhibited DPDPE stimulated PLC-p activation and, therefore, Ins(l,4,5)P3-dependent Ca2+ release and smooth muscle contraction in intestinal smooth muscle cells of the guinea pig [46]. However, the Ga... 

Ikeda K, Kobayashi T, Kumanishi T, Niki H, Yano R (2000) Involvement of G-protein-activated inwardly rectifying K (GIRK) channels in opioid-induced analgesia. Neurosci Res 38 113-116... 

Assays that measure the ability of ligands to inhibit voltage-activated Ca channels or to stimulate the activity of G protein-coupled inwardly rectifying K+ channels (GIRK). 

A G-protein-mediated effect has an absolute requirement for GTP. Reference has already been made to the requirement for GTP in reconstituting hormone-stimulated adenylate cyclase activity. A similar requirement can be demonstrated when the effector is an ion channel, such as the cardiac atrial inward-rectifier K+ channel which is activated following stimulation of the M2 muscarinic acetylcholine receptor. Thus, in the experiment illustrated in Figure 7.8, the channel recorded with a cell-... 

G, is the G-protein responsible for inhibiting adenylate cyclase. The inhibition is mediated by the a subunit. Unlike Gs, G, is not affected by CTx but instead is ADP-ribosylated (and inhibited) by PTx. Of the three isoforms of G, (Gn 3), an is the most potent inhibitor of cyclase. G, also activates inward-rectifier (Kir3.1/3.2 and Kir 3.1/3.4) K+ channels (GIRK channels), and this activation is mediated by released f v subunits (see below). 

Ma GH, Miller R, Kuznestov A et al. Kappa-opioid receptor activates an inwardly rectifying K+ channel by a G protein-linked mechanism coexpression in Xenopus oocytes. Mol Pharmacol 1995 47 1035-1040. 

In vivo studies employing tests of acute pain unequivocally showed the involvement of Katp, Kv1.1 and Ca2+-activated K+ channels in supraspinal, spinal and peripheral analgesia produced by different classes of analgesics. Furthermore, two-pore-domain and G-protein gated inward rectifier (Kir3.x) K+ channels are affected by volatile anesthetics. The latter also contribute to p- and K-opioid receptor-mediated analgesia (Ikeda et al., 2000). 

DeBock F, Kurz J, Azad SC, Parsons CG, Hapfelmeier G, et al. 2003. Alpha2-adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala Involvement of Gi/o-protein-mediated modulation of Ca2+-channels and inwardly rectifying K+-channels in LTD. Eur J Neurosci 17 1411-1424. 

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