Tetrodotoxin-resistant voltage-dependent sodium channels in identified muscle afferent neurons

Document Type

Article

Publication Title

Journal of Neurophysiology

Abstract

Muscle afferents are critical regulators of motor function (Group I and II) and cardiovascular responses to exercise (Group III and IV). However, little is known regarding the expressed voltage-dependent ion channels. We identified muscle afferent neurons in dorsal root ganglia (DRGs), using retrograde labeling to examine voltage-dependent sodium (NaV) channels. In patch-clamp recordings, we found that the dominant NaV current in the majority of identified neurons was insensitive to tetrodotoxin (TTX-R), with NaV current in only a few (14%) neurons showing substantial (>50%) TTX sensitivity (TTX-S). The TTX-R current was sensitive to a NaV1.8 channel blocker, A803467. Immunocytochemistry demonstrated labeling of muscle afferent neurons by a NaV1.8 antibody, which further supported expression of these channels. A portion of the TTX-R NaV current appeared to be noninactivating during our 25-ms voltage steps, which suggested activity of NaV1.9 channels. The majority of the noninactivating current was insensitive to A803467 but sensitive to extracellular sodium. Immunocytochemistry showed labeling of muscle afferent neurons by a NaV1.9 channel antibody, which supports expression of these channels. Further examination of the muscle afferent neurons showed that functional TTX-S channels were expressed, but were largely inactivated at physiological membrane potentials. Immunocytochemistry showed expression of the TTX-S channels NaV1.6 and NaV1.7 but not NaV1.1. NaV1.8 and NaV1.9 appear to be the dominant functional sodium channels in small- to medium-diameter muscle afferent neurons. The expression of these channels is consistent with the identification of these neurons as Group III and IV, which mediate the exercise pressor reflex. © 2012 the American Physiological Society.

First Page

2230

Last Page

2241

DOI

10.1152/jn.00219.2012

Publication Date

10-15-2012

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