Extracellular K+ Induces Locomotor-Like Patterns in the Rat Spinal Cord In Vitro: Comparison With NMDA or 5-HT Induced Activity

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Abstract
Bracci, E., M. Beato, and A. Nistri. Extracellular K+ induces locomotor-like patterns in the rat spinal cord in vitro: comparison with NMDA or 5-HT induced activity. J. Neurophysiol. 79: 2643–2652, 1998. 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 (∼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-d-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 μM) that were consistently slower than those induced by high K+ or NMDA. Ritanserin (1 μM) 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.