Sodium channel Na _v 1.6 is localized at nodes of Ranvier, dendrites, and synapses

Abstract

Voltage-gated sodium channels perform critical roles for electrical signaling in the nervous system by generating action potentials in axons and in dendrites. At least 10 genes encode sodium channels in mammals, but specific physiological roles that distinguish each of these isoforms are not known. One possibility is that each isoform is expressed in a restricted set of cell types or is targeted to a specific domain of a neuron or muscle cell. Using affinitypurified isoform-specific antibodies, we find that Na v1.6 is highly concentrated at nodes of Ranvier of both sensory and motor axons in the peripheral nervous system and at nodes in the central nervous system. The specificity of this antibody was also demonstrated with the Na v1.6-deficient mouse mutant strain med, whose nodes were negative for Nav1.6 immunostaining. Both the intensity of labeling and the failure of other isoform-specific antibodies to label nodes suggest that Na v1.6 is the predominant channel type in this structure. In the central nervous system, Nav1.6 is localized in unmyelinated axons in the retina and cerebellum and is strongly expressed in dendrites of cortical pyramidal cells and cerebellar Purkinje cells. Ultrastructural studies indicate that labeling in dendrites is both intracellular and on dendritic shaft membranes. Remarkably, Na v1.6 labeling was observed at both presynaptic and postsynaptic membranes in the cortex and cerebellum. Thus, a single sodium channel isoform is targeted to different neuronal domains and can influence both axonal conduction and synaptic responses.

Reduced Sodium Current in Purkinje Neurons from NaV1.1 Mutant Mice: Implications for Ataxia in Severe Myoclonic Epilepsy in Infancy

“…1A3). These results indicate that Na V 1.1 and Na V 1.6 are the predominant sodium channels in the cell bodies and dendrites of Purkinje neurons, in agreement with previous work (Westenbroek et al, 1989;Gong et al, 1999;Caldwell et al, 2000;Jenkins and Bennett, 2001;Schaller and Caldwell, 2003). The observed distribution of Na V channels in P13-P14 cerebellar neurons in our experiments indicates that Na V 1.1 and Na V 1.6 channels conduct nearly all sodium current in Purkinje neurons in this age range.…”

Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells

“…The kinetically fast and tetrodoxin-sensitive Na v 1.6 sodium channel is the dominant sodium channel at mature nodes (Caldwell et al, 2000). The newly constructed nodes of Ranvier on regenerated axons positioned between GFP internodes expressed Na v 1.6, but not Na v 1.2.…”

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

“…Immunocytochemical studies showed a high level of Nav1.2 immunoreactivity in the mossy fiber tract [83]. Furthermore, Nav1.2 and Nav1.6 immunoreactivity are often colocalized in nonmyelinated axons throughout the entire brain [18]. This suggests that native presynaptic channels in mossy fiber Fig.…”