title: Functional coupling of rat group II metabotropic glutamate receptors to an omega-conotoxin GVIA-sensitive calcium channel in human embryonic kidney 293 cells.
abstract: Metabotropic glutamate receptors are G protein-coupled receptors that perform a variety of modulatory roles in the central and peripheral nervous systems. The development of receptor subtype-specific agonists/antagonists has lagged far behind the isolation and characterization of receptor cDNAs. Further more, the coupling of specific metabotropic receptors to the various neuronal-specific effector molecules, such as voltage gated Ca2+ channels, has not been well studied. It was recently demonstrated that a rat group II metabotropic receptor (rm-GluR2) is capable of coupling to endogenous N-type Ca2+ channels when heterologously expressed in adult rat sympathetic ganglia neurons. To eventually understand the molecular aspects of metabotropic receptor modulation of the N-type Ca2+ channel, we have transiently expressed both group II receptors in a human embryonic kidney 293 cell line (G1A1) that stably expresses the human alpha 1B-1, alpha 2b, and beta 1-3 Ca2+ channel subunits. rmGluR2 and rmGluR3 modulate the omega-conotoxin GVIA-sensitive Ba2+ currents in G1A1 cells using a voltage-dependent mechanism via an endogenous pertussis toxin-sensitive G protein. Cell-attached "macropatch" recordings demonstrate that modulation by rmGluR2 and rmGluR3 is membrane delimited. This is the first report of Ca2+ channel modulation mediated by rmGluR3. In addition, an extensive pharmacological comparison between rmGluR2 and rmGluR3 reveals that these group II receptors interact with agonists and antagonists in unique ways.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. mccoolba@ctrvax.vanderbilt.edu
authors.forename: B A
authors.initials: BA
authors.lastname: McCool
authors.forename: J P
authors.initials: JP
authors.lastname: Pin
authors.forename: P F
authors.initials: PF
authors.lastname: Brust
authors.forename: M M
authors.initials: MM
authors.lastname: Harpold
authors.forename: D M
authors.initials: DM
authors.lastname: Lovinger
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism / Q000502:physiology*; D012680:Sensitivity and Specificity; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D018094:Receptors, Metabotropic Glutamate; D010566:Virulence Factors, Bordetella; D020866:omega-Conotoxin GVIA; D037342:Pertussis Toxin