QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (51) Citing Articles via Google Scholar Google Scholar Articles by Jeong, S.-W. Articles by Ikeda, S. R. Search for Related Content PubMed PubMed Citation Articles by Jeong, S.-W. Articles by Ikeda, S. R.

 Previous Article  |  Next Article 

The Journal of Neuroscience, June 15, 2000, 20(12):4489-4496

Endogenous Regulator of G-Protein Signaling Proteins Modify N-Type Calcium Channel Modulation in Rat Sympathetic Neurons

Seong-Woo Jeong and Stephen R. Ikeda

Laboratory of Molecular Physiology, Guthrie Research Institute, Sayre, Pennsylvania 18840

Experiments using heterologous overexpression indicate that regulator of G-protein signaling (RGS) proteins play important roles in G-mediated ion channel modulation. However, the roles subserved by endogenous RGS proteins have not been extensively examined because tools for functionally inhibiting natively expressed RGS proteins are lacking. To address this void, we used a strategy in which G_oA was rendered insensitive to pertussis toxin (PTX) and RGS proteins by site-directed mutagenesis. Either PTX-insensitive (PTX-i) or both PTX- and RGS-insensitive (PTX/RGS-i) mutants of G_oA were expressed along with G₁ and G₂ subunits in rat sympathetic neurons. After overnight treatment with PTX to suppress natively expressed G subunits, voltage-dependent Ca²⁺ current inhibition by norepinephrine (NE) (10 µM) was reconstituted in neurons expressing either PTX-i or PTX/RGS-i G_oA. When compared with neurons expressing PTX-i G_oA, the steady-state concentration-response relationships for NE-induced Ca²⁺ current inhibition were shifted to lower concentrations in neurons expressing PTX/RGS-i G_oA. In addition to an increase in agonist potency, the expression of PTX/RGS-i G_oA dramatically retarded the current recovery after agonist removal. Interestingly, the alteration in current recovery was accompanied by a slowing in the onset of current inhibition. Together, our data suggest that endogenous RGS proteins contribute to membrane-delimited Ca²⁺ channel modulation by regulating agonist potency and kinetics of G-protein-mediated signaling in neuronal cells.

Key words: calcium channel; G-protein; G; G; intranuclear injection; RGS protein; sympathetic neuron; voltage-dependent inhibition

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20124489-08$05.00/0

This article has been cited by other articles:

				M. J. Clark, J. J. Linderman, and J. R. Traynor Endogenous Regulators of G Protein Signaling Differentially Modulate Full and Partial {micro}-Opioid Agonists at Adenylyl Cyclase as Predicted by a Collision Coupling Model Mol. Pharmacol., May 1, 2008; 73(5): 1538 - 1548. [Abstract] [Full Text] [PDF]

				H. W. Tedford and G. W. Zamponi Direct G Protein Modulation of Cav2 Calcium Channels Pharmacol. Rev., December 1, 2006; 58(4): 837 - 862. [Abstract] [Full Text] [PDF]

				X. Huang, Y. Fu, R. A. Charbeneau, T. L. Saunders, D. K. Taylor, K. D. Hankenson, M. W. Russell, L. G. D'Alecy, and R. R. Neubig Pleiotropic Phenotype of a Genomic Knock-In of an RGS-Insensitive G184S Gnai2 Allele. Mol. Cell. Biol., September 1, 2006; 26(18): 6870 - 6879. [Abstract] [Full Text] [PDF]

				M. A. Clark and N. A. Lambert Endogenous Regulator of G-Protein Signaling Proteins Regulate the Kinetics of G{alpha}q/11-Mediated Modulation of Ion Channels in Central Nervous System Neurons Mol. Pharmacol., April 1, 2006; 69(4): 1280 - 1287. [Abstract] [Full Text] [PDF]

				Y. Fu, X. Huang, H. Zhong, R. M. Mortensen, L. G. D'Alecy, and R. R. Neubig Endogenous RGS Proteins and G{alpha} Subtypes Differentially Control Muscarinic and Adenosine-Mediated Chronotropic Effects Circ. Res., March 17, 2006; 98(5): 659 - 666. [Abstract] [Full Text] [PDF]

				A. Benians, M. Nobles, S. Hosny, and A. Tinker Regulators of G-protein Signaling Form a Quaternary Complex with the Agonist, Receptor, and G-protein: A NOVEL EXPLANATION FOR THE ACCELERATION OF SIGNALING ACTIVATION KINETICS J. Biol. Chem., April 8, 2005; 280(14): 13383 - 13394. [Abstract] [Full Text] [PDF]

				J. R. Traynor and R. R. Neubig REGULATORs OF G PROTEIN SIGNALING & DRUGS OF ABUSE Mol. Interv., February 1, 2005; 5(1): 30 - 41. [Abstract] [Full Text] [PDF]

				M. J. Clark and J. R. Traynor Endogenous Regulator of G Protein Signaling Proteins Reduce {micro}-Opioid Receptor Desensitization and Down-Regulation and Adenylyl Cyclase Tolerance in C6 Cells J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 809 - 815. [Abstract] [Full Text] [PDF]

				S. J. Bornheimer, M. R. Maurya, M. G. Farquhar, and S. Subramaniam Computational modeling reveals how interplay between components of a GTPase-cycle module regulates signal transduction PNAS, November 9, 2004; 101(45): 15899 - 15904. [Abstract] [Full Text] [PDF]

				M. J. Clark, R. R. Neubig, and J. R. Traynor Endogenous Regulator of G Protein Signaling Proteins Suppress G{alpha}o-Dependent, {micro}-Opioid Agonist-Mediated Adenylyl Cyclase Supersensitization J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 215 - 222. [Abstract] [Full Text] [PDF]

				A. C. Dolphin G Protein Modulation of Voltage-Gated Calcium Channels Pharmacol. Rev., December 1, 2003; 55(4): 607 - 627. [Abstract] [Full Text] [PDF]

				P. Tosetti, N. Pathak, M. H. Jacob, and K. Dunlap RGS3 mediates a calcium-dependent termination of G protein signaling in sensory neurons PNAS, June 10, 2003; 100(12): 7337 - 7342. [Abstract] [Full Text] [PDF]

				A. Benians, J. L. Leaney, and A. Tinker Agonist unbinding from receptor dictates the nature of deactivation kinetics of G protein-gated K+ channels PNAS, May 13, 2003; 100(10): 6239 - 6244. [Abstract] [Full Text] [PDF]

				J. Y. Zhou, P. T. Toth, and R. J. Miller Direct Interactions between the Heterotrimeric G Protein Subunit Gbeta 5 and the G Protein gamma Subunit-Like Domain-Containing Regulator of G Protein Signaling 11: Gain of Function of Cyan Fluorescent Protein-Tagged Ggamma 3 J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 460 - 466. [Abstract] [Full Text] [PDF]

				M. J. Clark, C. Harrison, H. Zhong, R. R. Neubig, and J. R. Traynor Endogenous RGS Protein Action Modulates {micro}-Opioid Signaling through Galpha o. EFFECTS ON ADENYLYL CYCLASE, EXTRACELLULAR SIGNAL-REGULATED KINASES, AND INTRACELLULAR CALCIUM PATHWAYS J. Biol. Chem., March 7, 2003; 278(11): 9418 - 9425. [Abstract] [Full Text] [PDF]

				H. Zhong, S. M. Wade, P. J. Woolf, J. J. Linderman, J. R. Traynor, and R. R. Neubig A Spatial Focusing Model for G Protein Signals. REGULATOR OF G PROTEIN SIGNALING (RGS) PROTEIN-MEDIATED KINETIC SCAFFOLDING J. Biol. Chem., February 21, 2003; 278(9): 7278 - 7284. [Abstract] [Full Text] [PDF]

				Y. Wang, G. Ho, J. J. Zhang, B. Nieuwenhuijsen, W. Edris, P. K. Chanda, and K. H. Young Regulator of G Protein Signaling Z1 (RGSZ1) Interacts with Galpha i Subunits and Regulates Galpha i-mediated Cell Signaling J. Biol. Chem., December 6, 2002; 277(50): 48325 - 48332. [Abstract] [Full Text] [PDF]

				P. Tosetti, T. Turner, Q. Lu, and K. Dunlap Unique Isoform of Galpha -interacting Protein (RGS-GAIP) Selectively Discriminates between Two Go-mediated Pathways That Inhibit Ca2+ Channels J. Biol. Chem., November 22, 2002; 277(48): 46001 - 46009. [Abstract] [Full Text] [PDF]

				S. Hollinger and J. R. Hepler Cellular Regulation of RGS Proteins: Modulators and Integrators of G Protein Signaling Pharmacol. Rev., September 1, 2002; 54(3): 527 - 559. [Abstract] [Full Text] [PDF]

				Q. Wang, M. Liu, B. Mullah, D. P. Siderovski, and R. R. Neubig Receptor-selective Effects of Endogenous RGS3 and RGS5 to Regulate Mitogen-activated Protein Kinase Activation in Rat Vascular Smooth Muscle Cells J. Biol. Chem., July 5, 2002; 277(28): 24949 - 24958. [Abstract] [Full Text] [PDF]

				J. Perroy, G. J. Gutierrez, V. Coulon, J. Bockaert, J.-P. Pin, and L. Fagni The C Terminus of the Metabotropic Glutamate Receptor Subtypes 2 and 7 Specifies the Receptor Signaling Pathways J. Biol. Chem., November 30, 2001; 276(49): 45800 - 45805. [Abstract] [Full Text] [PDF]

				H. Zhong and R. R. Neubig Regulator of G Protein Signaling Proteins: Novel Multifunctional Drug Targets J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 837 - 845. [Abstract] [Full Text]

				H. Chen and N. A. Lambert Endogenous regulators of G protein signaling proteins regulate presynaptic inhibition at rat hippocampal synapses PNAS, October 23, 2000; (2000) 230260397. [Abstract] [Full Text]

				C. B. Cooper, M. I. Arnot, Z.-P. Feng, S. E. Jarvis, J. Hamid, and G. W. Zamponi Cross-talk between G-protein and Protein Kinase C Modulation of N-type Calcium Channels Is Dependent on the G-protein beta Subunit Isoform J. Biol. Chem., December 22, 2000; 275(52): 40777 - 40781. [Abstract] [Full Text] [PDF]

				K.-L. Lan, H. Zhong, M. Nanamori, and R. R. Neubig Rapid Kinetics of Regulator of G-protein Signaling (RGS)-mediated Galpha i and Galpha o Deactivation. Galpha SPECIFICITY OF RGS4 AND RGS7 J. Biol. Chem., October 20, 2000; 275(43): 33497 - 33503. [Abstract] [Full Text] [PDF]

				H. Chen and N. A. Lambert Endogenous regulators of G protein signaling proteins regulate presynaptic inhibition at rat hippocampal synapses PNAS, November 7, 2000; 97(23): 12810 - 12815. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help