Expression of Nav1. 8 sodium channels perturbs the firing patterns of cerebellar Purkinje cells

M Renganathan, M Gelderblom, JA Black, SG Waxman - Brain research, 2003 - Elsevier
M Renganathan, M Gelderblom, JA Black, SG Waxman
Brain research, 2003Elsevier
The sensory neuron specific sodium channel Nav1. 8/SNS exhibits depolarized voltage-
dependence of inactivation, slow inactivation and rapid repriming, which differentiate it from
other voltage-gated sodium channels. Nav1. 8 is normally selectively expressed at high
levels in sensory ganglion neurons, but not within the CNS. However, expression of Nav1. 8
mRNA and protein are upregulated within cerebellar Purkinje cells in animal models of
multiple sclerosis (MS), and in human MS. To examine the effect of expression of Nav1. 8 on …
The sensory neuron specific sodium channel Nav1.8/SNS exhibits depolarized voltage-dependence of inactivation, slow inactivation and rapid repriming, which differentiate it from other voltage-gated sodium channels. Nav1.8 is normally selectively expressed at high levels in sensory ganglion neurons, but not within the CNS. However, expression of Nav1.8 mRNA and protein are upregulated within cerebellar Purkinje cells in animal models of multiple sclerosis (MS), and in human MS. To examine the effect of expression of Nav1.8 on the activity pattern of Purkinje cells, we biolistically introduced Nav1.8 cDNA into these cells in vitro. We report here that Nav1.8 can be functionally expressed at physiological levels (similar to the levels in DRG neurons where Nav1.8 is normally expressed) within Purkinje cells, and that its expression alters the activity of these neurons in three ways: first, by increasing the amplitude and duration of action potentials; second, by decreasing the proportion of action potentials that are conglomerate and the number of spikes per conglomerate action potential; and third, by contributing to the production of sustained, pacemaker-like impulse trains in response to depolarization. These results provide support for the hypothesis that the expression of Nav1.8 channels within Purkinje cells, which occurs in MS, may perturb their function.
Elsevier