Omega-conotoxin sensitivity and presynaptic inhibition of glutamatergic sensory neurotransmission in vitro.
Synaptic transmission between embryonic chick dorsal root ganglion (DRG) neurons and spinal cord neurons was studied in dissociated cell culture. Stimulation of DRG neurons evoked monosynaptic and polysynaptic excitatory responses in the spinal neurons. These responses could be reversibly blocked by application of 6-cyano-7-nitroquinoxaline-2,3-dione (a selective non-NMDA receptor antagonist) and irreversibly eliminated through the presynaptic action of omega-conotoxin GVIA (a selective N-type calcium channel antagonist). As N-type calcium channels in DRG neuron somata are targets for modulation via GABAB receptors, we tested the role of these receptors as regulators of synaptic transmission. Baclofen (a selective GABAB receptor agonist) reversibly inhibited synaptic transmission via a presynaptic, pertussis toxin-sensitive mechanism; CGP 35348 (a selective GABAB receptor antagonist) blocked the actions of baclofen. Taken together, these results demonstrate that N-type calcium channels play a dominant role in glutamatergic sensory neurotransmission. They suggest, in addition, that modulation of N-channel activity may underlie, at least in part, presynaptic inhibition of synaptic transmission between DRG neurons and their targets in the intact spinal cord.
Gruner
W
W
Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Silva
L R
LR
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D005071:Evoked Potentials / Q000187:drug effects; D058787:GABA-A Receptor Antagonists; D005727:Ganglia, Spinal / Q000502:physiology*; D008978:Mollusk Venoms / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D058787:GABA-A Receptor Antagonists; D008978:Mollusk Venoms; D009943:Organophosphorus Compounds; D010455:Peptides; D011810:Quinoxalines; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C066430:CGP 35348; D020866:omega-Conotoxin GVIA; D001418:Baclofen; D002118:Calcium