Effect of Hydrogen Peroxide and Glutamate on Muscle Spindle Afferent Receptor Ending Sensitivity to Muscle Stretch in Adult Mice

Abstract

Proprioception, or the sense of body position and movement, is required for the completion of complex motor tasks. Exercise impairs proprioception, although the mechanism for this is not well understood and likely involves changes to both peripheral signaling and central proprioceptive circuits. The Group Ia and II muscle spindle afferents (MSAs), which report muscle length and movement information to the central nervous system, are thought to be the primary proprioceptors. Substances released during exercise and activity, including reactive oxygen species and glutamate, have been shown to alter MSA activity in rats. Whether these substances alter MSA sensitivity via peripheral and/or central mechanisms is unclear. We tested the hypothesis that reactive oxygen species (hydrogen peroxide) and glutamate can act locally on MSA receptor endings and alter responsiveness to stretch. We used an in‐vitro mouse muscle‐nerve preparation to record MSA firing activity. Briefly, the extensor digitorum longus (EDL) muscle and innervating deep peroneal branch of the sciatic nerve were dissected and perfused in an oxygenated synthetic interstitial fluid tissue bath. An extracellular recording electrode was placed on the nerve and individual MSAs identified by waveform. A series of 4s ramp and hold stretches were applied to the EDL and instantaneous firing frequency before and during stretch was measured. Upon exposure to hydrogen peroxide (1 mM), there was an increase in static stretch response in 10 of 18 MSAs tested (n=9; 23 ± 13% increase). The remaining 8 MSAs showed no change in activity (n=9; 1.5 ± 2.8%). There was also an increase in individual afferent firing rates upon the addition of glutamate in a preliminary sample of MSAs (1 mM; n=4; 30 +/− 18% increase). These results support the hypothesis that hydrogen peroxide and glutamate can act locally in the absence of central nervous system circuits on MSA nerve endings to alter stretch sensitivity. However, not all MSAs respond to locally applied hydrogen peroxide, suggesting different sensitivities in subpopulations of MSAs.Support or Funding InformationThis work was supported by an SJSU RSCA award to KAW.