Signaling mechanisms of metabotropic glutamate receptor 5 subtype and its endogenous role in a locomotor network.
Metabotropic glutamate receptors (mGluRs) act as modulators in the CNS of vertebrates, but their role in motor pattern generation in particular is primarily unknown. The intracellular signaling mechanisms of the group I mGluRs (mGluR1 and mGluR5), and their endogenous role in regulating locomotor pattern generation have been investigated in the spinal cord of the lamprey. Application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) produced oscillations of the intracellular Ca2+ concentration ([Ca2+]i) in neurons. The oscillations were blocked by the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) but not by the mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester. These [Ca2+]i oscillations were abolished by a phospholipase C blocker and after depletion of internal Ca2+ stores by thapsigargin but did not involve protein kinase C activation. Furthermore, they were dependent on Ca2+ influx, because no [Ca2+]i oscillations were produced by DHPG in a Ca2+-free solution or after blockade of L-type Ca2+ channels. The mGluR5 is activated by an endogenous release of glutamate during locomotion, and a receptor blockade by MPEP caused an increase in the burst frequency. Thus, our results show that mGluR5 induces [Ca2+]i oscillations and regulates the activity of locomotor networks through endogenous activation.
Kettunen
Petronella
P
Nobel Institute for Neurophysiology, Department of Neuroscience, Retzius Laboratory, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Krieger
Patrik
P
Hess
Dietmar
D
El Manira
Abdeljabbar
A
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008124:Locomotion / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; D010738:Type C Phospholipases; D002118:Calcium