NaV1.7: Stress-induced changes in immunoreactivity within magnocellular neurosecretory neurons of the supraoptic nucleus

Molecular Pain

Stephen G Waxman³  Ingemar SJ Merkies²  Catharina G Faber¹  Janneke GJ Hoeijmakers¹  Joel A Black³ 

[1] Department of Neurology, University Medical Center Maastricht, Maastricht, the Netherlands;Department of Neurology, Spaarne Hospital, Hoofddorp, the Netherlands;Center for Neuroscience and Regeneration Research, Veterans Affairs Connecticut Healthcare System, West Haven, CT USA

关键词: Supraoptic nucleus;    Salt-loading;    Na_v1.7;    Hypothalamus;   

Others  :  862353
DOI  :  10.1186/1744-8069-9-39

 received in 2013-06-17, accepted in 2013-08-06,  发布年份 2013

【 摘 要 】

Background

Na_V1.7 is preferentially expressed, at relatively high levels, in peripheral neurons, and is often referred to as a “peripheral” sodium channel, and Na_V1.7-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 Na_V1.7 gain-of-function mutations and apparent hypothalamic dysfunction have appeared. The two sodium channels previously studied within the rat hypothalamic supraoptic nucleus, Na_V1.2 and Na_V1.6, display up-regulated expression in response to osmotic stress.

Results

Here we show that Na_V1.7 is present within vasopressin-producing neurons and oxytocin-producing neurons within the rat hypothalamus, and demonstrate that the level of Na_v1.7 immunoreactivity is increased in these cells in response to osmotic stress.

Conclusions

Na_V1.7 is present within neurosecretory neurons of rat supraoptic nucleus, where the level of immunoreactivity is dynamic, increasing in response to osmotic stress. Whether Na_V1.7 levels are up-regulated within the human hypothalamus in response to environmental factors or stress, and whether Na_V1.7 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 Na_V1.7 mutations, especially when subjected to stress, and for monitoring of hypothalamic function as Na_V1.7 blocking agents are studied.

【 授权许可】

   
2013 Black et al.; licensee BioMed Central Ltd.

【 图 表 】

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