Developmental regulation of the expression of sodium currents in Xenopus primary neurons

Abstract

The electrophysiological properties of neurons are determined by the expression of defined complements of ion channels. Nonetheless, the regulation mechanisms of the expression of neuronal ion channels are poorly understood, due in part to the diversity of neuron subtypes. We explored the expression of voltage-gated currents of Xenopus primary spinal neurons unequivocally identified by means of single-cell RT-PCR. We found that identified spinal neurons exhibit heterogeneity in the temporal appearance of voltage-gated currents. Nevertheless, all neurons progress to similar functional phenotypes. A physiological feature is the onset and increase of the expression of sodium currents. To understand the mechanisms underlying this process, we studied the effect of a dominant negative form of the transcriptional silencer REST/NRSF and found that it associates to an increase in the density of sodium currents. This observation is compatible with a role of this factor in the regulation of gene expression in neurons. These experiments constitute a proof of principle for the feasibility of analyzing molecular mechanisms of the regulation of ion channel genes during early neuronal development and provide direct evidence of the role of REST/NRSF in the control of neuronal sodium channel expression.