Inwardly-rectifying potassium channel

Inward Rectifier Potassium Channels or Kir Channels are a class of potassium channels generated by tetra-meiic arrangement of one-pore/two-transmembrane helix (1P/2TM) protein subunits, often associated with additional beta-subunits. Kir channels modulate cell excitability, being involved in repolarization of action potentials (see Fig. 1), setting the resting potential (see Fig. 1) of the cell, and contributing to potassium homeostasis. 

Nichols CG, Lopatin AN (1997) Inward rectifier potassium channels. Annu Rev Physiol 59 171-191... 

Activation of inwardly rectifying potassium channels Activation of MAP kinase... 

Abbreviations 3ARK1, -adrenergic receptor kinase 1 PLC, phospholipase C GIRK, G-protein-activated inwardly rectifying potassium channel Ca(N, P, Q), N-type, P-type, or Q-type calcium channel. 

Doupnik, C. A., Davidson, N. and Lester, H. A. The inward rectifier potassium channel family. Curr. Opin. Neurobiol. 5,268-277,1995. 

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. 

Other potassium channels also play important roles here. For example, Kv4.3/ KChIP complex conducts the transient outward current, Ito, responsible for the descending phase 1 of the cardiac action potential, whereas Kvl.5 is underlying the ultra rapid delayed rectifying current, IKur, responsible for descending phase 2. Finally, inward rectifier potassium channel (Kir2 family) is responsible for IKl current, which maintains the action potential close to or at the resting level (phase 4). 

G Protein-Activated Inward Rectifying Potassium Channel 2... 

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. 

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. 

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

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. 

Koyama M, Heerdt PM, Levi R (2003) Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors. Biochem Biophys Res Commun 306 792-6 Koyama S, Brodie MS, Appel SB (2007) Ethanol inhibition of M-current and ethanol-induced direct excitation of ventral tegmental area dopamine neurons. J Neurophysiol 97 1977-85 Kuzhikandathil EV, Yu W, Oxford GS (1998) Human dopamine D3 and D2l receptors couple to inward rectifier potassium channels in mammalian cell lines. Mol Cell Neurosci 12 390 102 Kuzhikandathil EV, Oxford GS (1999) Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. J Neurosci 19 1698-1707... 

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... 

Andersson, D. A., Zygmunt, P. M., Movahed, P., Andersson, T. L., and Hogestatt, E. D. 2000. Effects of inhibitors of small- and intermediate-conductance calcium-activated potassium channels, inwardly-rectifying potassium channels and Na(+)/K(+) ATPase on EDHF relaxations in the rat hepatic artery. Br. J. Pharmacol. 129 1490-1496. 

Hawkins, R.A., Jessy, J., Mans, A.M., De Joseph, M.R. (1993). Effect of reducing brain glutamine synthesis on metabolic symptoms of hepatic encephalopathy. J. Neurochem. 60, 1000-1006. Henderson, R.M., Graf, J., Boyer, J.L. (1989). Inward-rectifying potassium channels in rat hepatocytes. Am. J. Physiol. 256, G1028-G1035. 

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. 

Kuzhikandathil EV, Yu W, Oxford GS (1998) Human dopamine D3 and D2L receptors couple to inward rectifier potassium channels in mammalian cell lines. Mol Cell Neurosci 72 390-402. 

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. 

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