NaV1.7: stress-induced changes in immunoreactivity within magnocellular neurosecretory neurons of the supraoptic nucleus.
BACKGROUND
NaV1.7 is preferentially expressed, at relatively high levels, in peripheral neurons, and is often referred to as a "peripheral" sodium channel, and NaV1.7-specific blockers are under study as potential pain therapeutics which might be expected to have minimal CNS side effects. However, occasional reports of patients with NaV1.7 gain-of-function mutations and apparent hypothalamic dysfunction have appeared. The two sodium channels previously studied within the rat hypothalamic supraoptic nucleus, NaV1.2 and NaV1.6, display up-regulated expression in response to osmotic stress.


RESULTS
Here we show that NaV1.7 is present within vasopressin-producing neurons and oxytocin-producing neurons within the rat hypothalamus, and demonstrate that the level of Nav1.7 immunoreactivity is increased in these cells in response to osmotic stress.


CONCLUSIONS
NaV1.7 is present within neurosecretory neurons of rat supraoptic nucleus, where the level of immunoreactivity is dynamic, increasing in response to osmotic stress. Whether NaV1.7 levels are up-regulated within the human hypothalamus in response to environmental factors or stress, and whether NaV1.7 plays a functional role in human hypothalamus, is not yet known. Until these questions are resolved, the present findings suggest the need for careful assessment of hypothalamic function in patients with NaV1.7 mutations, especially when subjected to stress, and for monitoring of hypothalamic function as NaV1.7 blocking agents are studied.
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Joel A
JA
Black
Janneke G J
JG
Hoeijmakers
Catharina G
CG
Faber
Ingemar S J
IS
Merkies
Stephen G
SG
Waxman
D000818:Animals; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009997:Osmotic Pressure / Q000502:physiology*; D010146:Pain / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000378:metabolism*; D015854:Up-Regulation
D062557:NAV1.6 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; C507811:Scn8a protein, rat; C503480:Scn9a protein, rat