Participation of excitatory amino acid receptors in the slow excitatory synaptic transmission in rat spinal dorsal horn.
In a rat spinal slice preparation the participation of excitatory amino acid (EAA) receptors in the responses of deep dorsal horn neurons to repetitive stimulation of lumbar dorsal roots was investigated using 3 EAA receptor antagonists, kynurenic acid, D-(-)-2-amino-4-phosphonovaleric acid (D-APV) and 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) and current-clamp and voltage-clamp techniques. We found that the slow excitatory synaptic response evoked by 10-20 Hz electrical stimulation of primary afferent fibers consisted of two depolarizing components: an initial component lasting 1-5 s and a late one of 1-3 min duration. The initial and late components of the slow excitatory synaptic response can also be distinguished on the basis of their voltage-dependence and sensitivity to Mg2+ ions, kynurenate, D-APV and CNQX. In the presence of Mg2+, the initial component of the slow excitatory synaptic response increased with membrane hyperpolarization, whereas the late component decreased in most of the cells examined. In a zero-Mg2+ medium, the initial component was potentiated, but the late component was reduced. In both transverse and longitudinal spinal cord slices perfused with 1.2 mM Mg(2+)-containing medium, bath application of kynurenic acid (0.1-0.5 mM), D-APV (0.05-0.1 mM) and CNQX (5-7 microM) caused a reversible reduction of the peak amplitude of the initial slow depolarizing component that was greater in transverse (kynurenic acid: by 92.6 +/- 5.0%; D-APV: by 69.1 +/- 7.8%; CNQX: by 76.6 +/- 9.8%) than in longitudinal slices (kynurenic acid: by 53.3 +/- 1.3%; D-APV: by 31.5 +/- 9.1%; CNQX: by 35.3 +/- 11.1%). In contrast, all 3 antagonists of EAA receptors produced no consistent change in the peak amplitude or half-duration of the late depolarizing component of the slow excitatory synaptic response. Our results obtained with EAA receptor antagonists, at resting membrane potentials, in the absence and presence of Mg2+ and synaptic inhibition, indicate that the synaptic activation of the NMDA- and non-NMDA-receptor systems of deep spinal dorsal horn neurons by repetitive stimulation of primary afferent fibers may be selectively involved in the mediation of the initial, but not the late depolarizing component of the slow excitatory synaptic response.
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.
G
G
Gerber
R
R
Cerne
M
M
Randić
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials; D005260:Female; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D000596:Amino Acids; D018377:Neurotransmitter Agents; D011810:Quinoxalines; D017981:Receptors, Neurotransmitter; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; D008274:Magnesium