4.4 Article

NaV1.9 channels in muscle afferent neurons and axons

期刊

JOURNAL OF NEUROPHYSIOLOGY
卷 120, 期 3, 页码 1032-1044

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00573.2017

关键词

A803467; axon channels; exercise pressor reflex; immunohistochemistry patch clamp

资金

  1. Graduate Program Committee of the Kirksville College of Osteopathic Medicine, A. T. Still University of Health Sciences
  2. National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR-059397]

向作者/读者索取更多资源

The exercise pressor reflex (EPR) is activated by muscle contractions to increase heart rate and blood pressure during exercise. While this reflex is beneficial in healthy individuals, the reflex activity is exaggerated in patients with cardiovascular disease, which is associated with increased mortality. Group III and IV afferents mediate the EPR and have been shown to express both tetrodotoxin-sensitive (TTX-S, Na(V)1.6, and Na(V)1.7) and -resistant (TTX-R, Na(V)1.8, and Na(V)1.9) voltage-gated sodium (Na-V) channels, but Na(V)1.9 current has not yet been demonstrated. Using a F--containing internal solution, we found a Na-V current in muscle afferent neurons that activates at around -70 mV with slow activation and inactivation kinetics, as expected from Na(V)1.9 current. However, this current ran down with time, which resulted, at least in part, from increased steady-state inactivation since it was slowed by both holding potential hyperpolarization and a depolarized shift of the gating properties. We further show that, following Na(V)1.9 current rundown (internal F-), application of the Na(V)1.8 channel blocker A803467 inhibited significantly more TTX-R current than we had previously observed (internal Cl-), which suggests that Na(V)1.9 current did not rundown with that internal solution. Using immunohistochemistry, we found that the majority of group IV somata and axons were Na(V)1.9 positive. The majority of small diameter myelinated afferent somata (putative group III) were also Na(V)1.9 positive, but myelinated muscle afferent axons were rarely labeled. The presence of Na(V)1.9 channels in muscle afferents supports a role for these channels in activation and maintenance of the EPR. NEW & NOTEWORTHY Small diameter muscle afferents signal pain and muscle activity levels. The muscle activity signals drive the cardiovascular system to increase muscle blood flow, but these signals can become exaggerated in cardiovascular disease to exacerbate cardiac damage. The voltage-dependent sodium channel Na(V)1.9 plays a unique role in controlling afferent excitability. We show that Na(V)1.9 channels are expressed in muscle afferents, which supports these channels as a target for drug development to control hyperactivity of these neurons.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据