Abstract

A class of Group III muscle afferent neurons has branching sensory terminals in the connective tissue between layers of mouse abdominal muscles (“CT3 muscle afferents”). These sensory endings are both mechanosensitive and metabosensitive. In the present study, responses of CT3 afferents to lactate ions and changes in temperature were recorded. Raising muscle temperature from 32.7°C to 37°C had no consistent effects on CT3 afferent basal firing rate or responses to either von Frey hair stimulation or to an applied load. Superfusion with lactate ions (15 mM, pH 7.4) was associated with an increase in firing from 6 ± 0.7 Hz to 11.7 ± 6.7 Hz (14 units, n = 13, P < 0.05, P = 0.0484) but with considerable variability in the nature and latency of response. Reducing the concentration of extracellular divalent cations, which mimicked the chelating effects of lactate, did not increase firing. Raised concentrations of divalent cations (to compensate for chelation) did not block excitatory effects of lactate on CT3 afferents, suggesting that effects via ASIC3 were not involved. Messenger RNA for the G-protein coupled receptor, hydroxyl carboxylic acid receptor 1 (HCAR1) was detected in dorsal root ganglia and HCAR1-like immunoreactivity was present in spinal afferent nerve cell bodies retrogradely labeled from mouse abdominal muscles. HCAR1-like immunoreactivity was also present in axons in mouse abdominal muscles. This raises the possibility that some effects of lactate on group III muscle afferents may be mediated by HCAR1.

Highlights

  • Striated muscle is innervated by multiple classes of sensory neurons with a range of properties

  • The present study suggests that lactate may contribute, via its specialized receptor, as lactate, applied without adenosine triphosphate (ATP) or protons, activated many connective tissue group III muscle afferent (CT3) afferent endings

  • We demonstrated that CT3 afferents are activated by physiological concentrations of lactate

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Summary

Introduction

Striated muscle is innervated by multiple classes of sensory neurons with a range of properties. Group III and IV fibers are smaller in diameter, with slower conduction and encode mechanosensitive, metabosensitive and nociceptive signals from muscle. A class of group III mechanosensitive afferents was recently characterized in detail and shown to have endings in the Abbreviations: ATP, adenosine triphosphate; CGRP, calcitonin gene-related peptide; CT3, connective tissue group III muscle afferent; DMSO, dimethyl sulphoxide; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; GPR81, G protein-coupled receptor 81; HCAR1, hydroxyl carboxylic acid receptor 1; NF200, Neurofilament 200; PBS, phosphate-buffered saline. Effects of Lactate on Muscle Metaboreceptors connective tissue layers closely associated with muscle fibers, and were both mechanosensitive and metabosensitive. These were referred to as ‘‘CT3’’ afferents. PH changes are often detected in sensory endings via ASIC channels, ASIC3 (Molliver et al, 2005; Naves and McCleskey, 2005; Gregory et al, 2015)

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