Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones

  • Kuo J
  • Lee R
  • Zhang L
 et al. 
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Spinal motoneurons, like many neurons, respond with repetitive spiking to sustained inputs. The afterhyperpolarization (AHP) that follows each spike, however, decays relatively slowly in motoneurons. The slow depolarization during this decay should allow sodium (Na+) channel inactivation to keep up with its activation and thus should prevent initiation of the next spike. We hypothesized that the persistent component of the total Na+ current provides the mechanism that generates a rate of rise sufficiently rapid to generate a spike. In large cultured spinal neurons, presumed to be primarily motoneurons, inhibition of persistent sodium current (NaP) by the drug riluzole at low concentrations resulted in a loss of repetitive firing. However, cells remained fully capable of producing spikes to transient inputs. These effects of riluzole were not due to insufficient depolarization, enhancement of the AHP, or sustained Na+ channel inactivation. To further test this hypothesis, computer simulations were performed with a kinetic Na+ channel model that provided greater independent control of NaP relative to transient Na+ current (NaT) than that provided by riluzole administration. The model was tuned to generate substantial NaP and exhibited good repetitive firing to slowly rising inputs. When NaP was sharply reduced without significantly altering NaT, the model reproduced the effects of riluzole administration, inducing failure of repetitive firing but allowing single spikes in response to sharp transients. These results strongly support the essential role of NaP in spike initiation to slow inputs in spinal neurons. NaP may play a fundamental role in determining how a neuron responds to sustained inputs.

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  • J. J. Kuo

  • R. H. Lee

  • L. Zhang

  • C. J. Heckman

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