Protein gates

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... 

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. 

In Phase I clinical trials with stable renal transplant patients, FTY720 led to a transient reduction in the number of circulating lymphocytes whilst being well-tolerated. Treatment was associated with a mild reduction in heart rate that was maximal 6 h after the first dose and returned to baseline with continuous treatment [52,53]. The mild effect on heart rate is believed to arise from SlPj and/or SlP3-mediated activation of G-protein-gated inwardly rectifying potassium (GIRK) channels in atrial myocytes [54-56]. 

Zhou W et al Mechanism underlying bupivacaine inhibition of G protein-gated inwardly rectifying K+ channels. Proc Natl Acad Sci USA 2001 98 6482. [PMID 11353868]... 

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). 

Jeong, H.-J., Han, S.-H., Min, B.-l., Cho, Y.-W. 5-HT1A receptor-mediated activation of G-protein-gated inwardly rectifying kC current in rat periaqueductal gray neurons, Neuropharmacology 2001, 41, 175-185. 

Weigl, L. G. and Schreibmayer, W. G protein-gated inwardly rectifying potassium channels are targets for volatile anesthetics, Molecular Pharmacology 2001, 60, 282-289. 

Marker CL, Lujan R, Loh HH, Wickman K. Spinal G-protein-gated potassium channels contribute in a dose-dependent manner to the analgesic effect of mu-and delta- but not kappa-opioids. J Neurosci. 2005 25 3551-3559. 

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... 

Pieribone VA, Porton B, Rendon B et al (2002) Expression of synapsin III in nerve terminals and neurogenic regions of the adult brain. J Comp Neurol 454 105-14 Ponce A, Bueno E, Kentros C et al (1996) G-protein-gated inward rectifier K+ channel proteins (GIRK1) are present in the soma and dendrites as well as in nerve terminals of specific neurons in the brain. J Neurosci 16 1990-2001... 

Saitoh O, Masuho I, Terakawa I et al (2001) Regulator of G protein signaling 8 (RGS8) requires its NH2 terminus for subcellular localization and acute desensitization of G protein-gated K+ channels. J Biol Chem 276 5052-8... 

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... 

Brown AM, Birnbauemr L. 1988. Direct G protein gating of ion channels. Am J Physiol 254 H401-H410. 

Fig. 13. Characteristics of activation of a G protein-gated K+ channel as seen in endocrine (GH3) cells. Panel a, activation of the channel by 100 /u,M GTP-yS panel b, activation of the K+ channel by 2 nM GTP-activated Gk (Gk ) panel c, dependence of K+ channel activation by receptors (10 /u.M acetylcholine, ACh) on GTP (when present 100 /xM) panel d, sensitivity of GH, cell Gk to uncoupling by PTX, lack of effect of 2 nM GTP S-activated Gs (Gs ) and reconstitution of receptor (somatostatin, SST)-K channel coupling by exogenously added native Gk (2 nM) in the presence of 100 juM GTP (W, wash) panel e, effect of ak , i.c., ak-GTPyS resolved from fiy dimers, added at 0.5, 5 and 25 pM panel f, lack of effect of fiy dimers on K+ conductance of an ak responsive membrane. For rest of conditions see legend to Fig. 4 and Refs. 144, 145 and 232.

Inanobe A, Yoshimoto Y, Horio Y, Morishige KI, Hibino H, Matsumoto S, Tokunaga Y, Maeda T, Hata Y, Takai Y, Kurachi Y (1999) Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra. J Neurosci 79 1006-1017. 

Davila V, Yan Z, Craciun LC, Logothetis D, Sulzer D (2003) D3 dopamine autoreceptors do not activate G-protein-gated inwardly rectifying potassium channel currents in substantia nigra dopamine neurons. J Neurosci 23 5693-5697. 

Voltage and G-protein-gated channels K ch and Km (6 helices) quite similar to Ky(s) and Ky(r), but which interact with Gi proteins coupled to M2 muscarinic acetylcholine receptors, or with Gq proteins coupled to M3 receptors, respectively. Stimulation of M2 or M3 muscarinic receptors by acetylcholine in pacemaker cardiac... 

Nishida, M., and MacKinnon, R. (2002) Structural basis of inward rectification Cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8.ANG. resolution. Cell 111,957-965. 

GIRK = G protein-gated inwardly rectifying potassium channel... 

How long it takes for a protein to bind or release a small molecule may depend on the time required for the protein to open or close a cleft. Similarly, the protein "gates" that pass molecules and ions through membranes rapidly change from open to closed states. The dynamic behavior of proteins is at least as important in their function as the static details of their structure. 

The Oj receptors (and and receptors (and are GPCRs. receptors couple to a variety of effectors (Table 6-6), generally inhibiting adenylyl cyclase and activating G protein-gated channels, resulting in membrane hyperpolarization (possibly via Ca -dependent processes or from direct interaction of liberated /3y subunits with channels). 

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