Experimental and modeling studies of novel bursts induced by blocking na(+) pump and synaptic inhibition in the rat spinal cord.

This study addressed some electrophysiological mechanisms enabling neonatal rat spinal networks in vitro to generate spontaneous rhythmicity. Networks, made up by excitatory connections only after block of GABAergic and glycinergic transmission, develop regular bursting (disinhibited bursts) suppressed by the Na(+) pump blocker strophanthidin. Thus the Na(+) pump is considered important to control bursts. This study, however, shows that, after about 1 h in strophanthidin solution, networks of the rat isolated spinal cord surprisingly resumed spontaneous bursting ("strophanthidin bursting"), which consisted of slow depolarizations with repeated oscillations. This pattern, recorded from lumbar ventral roots, was synchronous on both sides, of irregular periodicity, and lasted for > or =12 h. Assays of (86)Rb(+) uptake by spinal tissue confirmed Na(+) pump block by strophanthidin. The strophanthidin rhythm was abolished by glutamate receptor antagonists or tetrodotoxin, indicating its network origin. N-methyl-D-aspartate (NMDA), serotonin, or high K(+) could not accelerate it. The size of each burst was linearly related to the length of the preceding pause. Bursts could also be generated by dorsal root electrical stimulation and possessed similar dependence on the preceding pause. Conversely, disinhibited bursts could be evoked at short intervals from the preceding one unless repeated pulses were applied in close sequence. These data suggest that rhythmicity expressed by excitatory spinal networks could be controlled by Na(+) pump activity or slow synaptic depression. A model based on the differential time course of pump operation and synaptic depression could simulate disinhibited and strophanthidin bursting, indicating two fundamental, activity-dependent processes for regulating network discharge.