Extracellular K+ induces locomotor-like patterns in the rat spinal cord in vitro: comparison with NMDA or 5-HT induced activity.
Bath-application of increasing concentrations of extracellular K+ elicited alternating motor patterns recorded from pairs of various lumbar ventral roots of the neonatal rat (0-2 days old) spinal cord in vitro. The threshold concentration of K+ for this effect was 7.9 +/- 0.8 mM (mean +/- SD). The suprathreshold concentration range useful to evoke persistent motor patterns (lasting >/=10 min) was very narrow ( approximately 1 mM) as further increments elicited only rhythmic activity lasting from 20 s to a few minutes. On average, the fastest period of rhythmic patterns was 1.1 +/- 0.3 s. Intracellular recording from lumbar motoneurons showed that raised extracellular K+ elicited membrane potential oscillations with superimposed repetitive firing. In the presence of N-methyl--aspartate (NMDA) or non-NMDA receptor blockers [R(-)-2-amino-phosphonovaleric acid or 6-cyano-7-nitroquinoxaline-2,3-dione, respectively] extracellular K+ increases could still induce motor patterns although the threshold concentration was raised. Serotonin (5-HT) also induced alternating motor patterns (threshold 15 +/- 7 microM) that were consistently slower than those induced by high K+ or NMDA. Ritanserin (1 microM) prevented the locomotor-like activity of 5-HT but not that of high K+ provided the concentration of the latter was further increased. Subthreshold concentrations of K+ became effective in the presence of subthreshold doses of 5-HT or NMDA, indicating mutual facilitation between these substances. The fastest pattern frequency was observed by raising K+ or by adding NMDA. In the presence of 5-HT, the pattern frequency was never as fast even if NMDA (or high K+) was coapplied. Furthermore, application of 5-HT significantly slowed down the K+- or NMDA-induced rhythm, an effect strongly potentiated in the presence of ritanserin. It is suggested that the operation of the spinal locomotor network was activated by rises in extracellular K+, which presumably led to a broad increase in neuronal excitability. Whenever the efficiency of excitatory synaptic transmission was diminished (for example by glutamate receptor antagonism), a larger concentration of K+ was required to evoke locomotor-like patterns. The complex effect (comprising stimulation and inhibition) of 5-HT on alternating pattern generation appeared to result from a dual action of this substance on the spinal locomotor network.
Bracci
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Biophysics Sector and Instituto Nazionale di Fisica della Materia Unit, International School for Advanced Studies (SISSA), 34013 Trieste, Italy.
Beato
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Nistri
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010507:Periodicity; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D012701:Serotonin; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D011188:Potassium