Abstract
Aim:
G protein-coupled inwardly rectifying potassium channels (GIRK) are important for neuronal signaling and membrane excitability. In the present study, we intend to find whether GIRK channels express functionally in adult rat dorsal root ganglion (DRG) neurons.
Methods:
We used RT-PCR to detect mRNA for 4 subunits of GIRK in the adult DRG. The whole-cell patch clamp recording was used to confirm GIRK channels functionally expressed.
Results:
The mRNA for the 4 subunits of GIRK were detected in the adult DRG. GTPĪ³S enhanced inwardly rectifying potassium (K+) currents of the DRG neurons, while Ba2+ inhibited such currents. Furthermore, the GIRK channels were shown to be coupled to the GABAB receptor, a member of the G protein-coupled receptor family, as baclofen increased the inwardly rectifying K+ currents.
Conclusion:
GIRK channels are expressed and functionally coupled with GABAB receptors in adult rat DRG neurons.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Mark, MD, Herlitze S . G-protein mediated gating of inward-rectifier K+channels. Eur J Biochem 2000; 19: 5830ā6.
Logothetis DE, Kurachi Y, Galper J, Neer EJ, Clapham DE . The beta gamma subunits of GTP-binding proteins activate the muscarinic K+channel in heart. Nature 1987; 6102: 321ā6.
He C, Zhang H, Mirshahi T, Logothetis DE . Identification of a potassium channel site that interacts with G protein beta gamma subunits to mediate agonist-induced signaling. J Biol Chem 1999; 18: 1251ā74.
He C, Yan X, Zhang H, Mirshahi T, Jin T, Huang A, et al. Identification of critical residues controlling G protein-gated inwardly rectifying K+channel activity through interactions with the beta gamma subunits of G proteins. J Biol Chem 2002; 8: 6088ā96.
Sodickson DL, Bean BP . Neurotransmitter activation of inwardly rectifying potassium current in dissociated hippocampal CA3 neurons: Interactions among multiple receptors. J Neurosci 1998; 20: 8153ā62.
Yamada M, Inanobe A, Kurachi Y . G protein regulation of potassium ion channels. Pharmacol Rev 1998; 4: 723ā57.
Karschin A . G protein regulation of inwardly rectifying K+channels. News Physiol Sci 1999; 14: 215ā20.
Hille B . Ionic channels of excitable membranes, 2nd ed. Sunderland, MA: Sinauer Associates; 1992.
Krapivinsky G, Gordon EA, Wickman K, Velimirovic B, Krapivinsky L, Clapham DE . The G-protein-gated atrial K+channel I KACh is a heteromultimer of two inwardly rectifying K+channel proteins. Nature 1995; 6518: 135ā41.
Wickman K, Nemec J, Gendler SJ, Clapham DE . Abnormal heart rate regulation in GIRK4 knockout mice. Neuron 1998; 1: 103ā14.
Tomoko T, Christian A . Phasic and tonic attenuation of EPSPs by inward rectifier K+channels in rat hippocampal pyramidal cells. J Physiol 2002; 539 (Pt 1): 67ā75.
McCleskey EW, Gold MS . Ion channels of nociception. Annu Rev Physiol 1999; 61: 835ā56.
Shaqura MA, Zollner C, Mousa SA, Stein C, Schafer M . Characterization of Ī¼ opioid receptor binding and G protein coupling in rat hypothalamus, spinal cord, and primary afferent neurons during inflammatory pain. J Pharmacol Exp Ther 2004; 2: 7121ā8.
Towers S, Princivalle A, Billinton A, Edmunds M, Bettler B, Urban L, et al. GABAB receptor protein and mRNA distribution in rat spinal cord and dorsal root ganglia. Eur J Neurosci 2000; 9: 3201ā10.
Yang Q, Wu ZZ, Li X, Li ZW, Wei JB, Hu QS . Modulation by oxytocin of ATP-activated currents in rat dorsal root ganglion neurons. Neuropharmacology 2002; 5: 910ā6.
Chen H, Ikeda SR . Modulation of ion channels and synaptic transmission by a human sensory neuron-specific G-protein-coupled receptor, SNSR4/mrgX1, heterologously expressed in cultured rat neurons. J Neurosci 2004; 21: 5044ā53.
Yagi J, Sumino R . Inhibition of a hyperpolarization-activated current by clonidine in rat dorsal root ganglion neurons. J Neurophysiol 1998; 3: 1094ā104.
Andrade R, Malenka RC, Nicoll RA . A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science 1986; 4781: 1261ā5.
Karschin CW, Schreibmayer N, Dascal H, Lester N, Davidson A . Karschin. Distribution and localization of a G protein-coupled inwardly rectifying K+channel in the rat. FEBS Lett 1994; 348: 139ā44.
Li JH, You ZD, Song CY, Lu CL, He C . The expression of G-protein-gated inwardly rectifying K+channels GIRK1 and GIRK2 mRNAs in the supraoptic nucleus of the rat and possible role involved. Neuroreport 2001; 5: 1007ā10.
Karschin C, Dissmann E, Stuhmer W, Karschin A . IRK(1ā3) and GIRK(1ā4) inwardly rectifying K+channel mRNAs are differentially expressed in the adult rat brain. J Neurosci 1996; 11: 3559ā70.
Mitrovic I, Margeta-Mitrovic M, Bader S, Stoffel M, Jan LY, Basbaum AI . Contribution of GIRK2-mediated postsynaptic signaling to opiate and alpha2-adrenergic analgesia and analgesic sex differences. Proc Natl Acad Sci USA 2003; 100: 271ā6.
Kanjhan R, Coulson EJ, Adams DJ, Bellingham MC . Tertiapin-Q blocks recombinant and native large conductance K+channels in a use-dependent manner. J Pharmacol Exp Ther 2005; 314: 1353ā61.
Karschin C, Karschin A . Ontogeny of gene expression of Kir channel subunits in the rat. Mol Cell Neurosci 1997; 10: 131ā48.
Luscher C, Jan LY, Stoffel M, Malenka RC, Nicoll RA . G protein coupled inwardly rectifying K+channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron 1997; 19: 687ā95.
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: 3551ā9.
Williams J, Zieglgansberger W . Mature spinal ganglion cells are not sensitive to opiate receptor mediated actions. Neurosci Lett 1981; 21: 211ā6.
Menon-Johansson AS, Berrow N, Dolphin AC . G(o) transduces GABAB-receptor modulation of N-type calcium channels in cultured dorsal root ganglion neurons. Pflugers Arch 1993; 425: 335ā43.
Tatebayashi H, Ogata N . Kinetic analysis of the GABAB-medi-ated inhibition of the high-threshold Ca2+current in cultured rat sensory neurons. J Physiol 1992; 447: 391ā407.
Green KA, Cottrell GA . Actions of baclofen on components of the Ca-current in rat and mouse DRG neurons in culture. Br J Pharmacol 1988; 94: 235ā45.
Holz GG IV, Kream RM, Spiegel A, Dunlap K . G proteins couple alpha-adrenergic and GABAb receptors to inhibition of peptide secretion from peripheral sensory neurons. J Neurosci 1989; 9: 657ā66.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by the National Natural Science Foundation of China (No 30370454, 30325022 and 30530240), the National Key Basic Research Program (No 2006CB500702), Program for Changjiang Scholars and Innovative Research Team in University, Shanghai Metropolitan Fund for Research and Development (No 04DZ14005 and 04XD14004).
Rights and permissions
About this article
Cite this article
Gao, Xf., Zhang, Hl., You, Zd. et al. G protein-coupled inwardly rectifying potassium channels in dorsal root ganglion neurons. Acta Pharmacol Sin 28, 185ā190 (2007). https://doi.org/10.1111/j.1745-7254.2007.00478.x
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1111/j.1745-7254.2007.00478.x
