GABA-receptor-independent dorsal root afferents depolarization in the neonatal rat spinal cord.
Dorsal root afferent depolarization and antidromic firing were studied in isolated spinal cords of neonatal rats. Spontaneous firing accompanied by occasional bursts could be recorded from most dorsal roots in the majority of the cords. The afferent bursts were enhanced after elevation of the extracellular potassium concentration ([K+]e) by 1-2 mM. More substantial afferent bursts were produced when the cords were isolated with intact brain stems. Rhythmic afferent bursts could be recorded from dorsal roots in some of the cords during motor rhythm induced by bath-applied serotonin and N-methyl--aspartate (NMDA). Bilaterally synchronous afferent bursts were produced in pairs of dorsal roots after replacing the NaCl in the perfusate with sodium-2-hydroxyethansulfonate or after application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline with or without serotonin (5-HT) and NMDA. Antidromic afferent bursts also could be elicited under these conditions by stimulation of adjacent dorsal roots, ventrolateral funiculus axons, or ventral white commissural (VWC) fibers. The antidromic bursts were superimposed on prolonged dorsal root potentials (DRPs) and accompanied by a prolonged increase in intraspinal afferent excitability. Surgical manipulations of the cord revealed that afferent firing in the presence of bicuculline persisted in the hemicords after hemisection and still was observed after removal of their ventral horns. Cutting the VWC throughout its length did not perturb the bilateral synchronicity of the discharge. These findings suggest that the activity of dorsal horn neurons is sufficient to produce the discharge and that the bilateral synchronicity can be maintained by cross connectivity that is relayed from side to side dorsal to the VWC. Antagonists of GABAB, 5-HT2/5-HT1C, or glutamate metabotropic group II and III receptors could not abolish afferent depolarization in the presence of bicuculline. Depolarization comparable in amplitude to DRPs, could be produced in tetrodotoxin-treated cords by elevation of [K+]e to the levels reported to develop in the neonatal rat spinal cord in response to dorsal root stimulation. A mechanism involving potassium transients produced by neuronal activity therefore is suggested to be the major cause of the GABA-independent afferent depolarization reported in our study. Possible implications of potassium transients in the developing and the adult mammalian spinal cord are discussed.
Kremer
E
E
Department of Anatomy and Cell Biology, The Hebrew University Medical School, Jerusalem 91120, Israel.
Lev-Tov
A
A
D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000502:physiology; D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D018684:Glycine Agents / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007513:Isethionic Acid / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D018079:Receptors, GABA / Q000502:physiology*; D017470:Receptors, Glutamate / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
C089836:2-amino-2-methyl-4-phosphonobutyrate; C074680:2-amino-4-phosphonobutanoic acid receptor; C089837:2-methyl-2-(2-carboxycyclopropyl)glycine; D000600:Amino Acids, Dicarboxylic; D000613:Aminobutyrates; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018684:Glycine Agents; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D012702:Serotonin Antagonists; D012701:Serotonin; D016202:N-Methylaspartate; D007513:Isethionic Acid; D001418:Baclofen; D013331:Strychnine; D011188:Potassium; C057491:2-hydroxysaclofen; D008784:Methysergide; D001640:Bicuculline