Figure 6.

Whrn facilitates pSN stretch-evoked activity independently from a glutamate-based mechanism of pSN sensitization to muscle stretch. A, Influence of glutamate on wild-type and wi/wi mutant Sol pSN firing rates. Schematics of pSN sensory endings illustrating that endogenous (control) or exogenous glutamate (+Glut.) increases pSN sensitivity to stretch (illustrated by an increase in the number of stretch-sensitive mechanotransduction channels [MTC]; the actual mechanism has yet to be determined). B, Representative recordings of wild-type and wi/wi mutant Sol muscles nerves in the absence (top) and presence of 10 nm glutamate (bottom). C, Quantification of spontaneous discharge activity in wild-type (blue) and wi/wi mutant (red) Sol pSNs in the presence of increasing concentrations of glutamate. Rather than increasing pSN baseline excitability, glutamate appears to dampen spontaneous activity levels. D, NEA in pSNs of wild-type (blue) and wi/wi mutant (red) Sol muscles in the presence of increasing amounts of glutamate. In both wild-type and wi/wi mutants, glutamate results in an increased afferent firing rate (mean NEA ± SEM without glut, 10 nm glut, 100 nm glut, 1 μm glut for wt: 106.0 ± 12.4 imp/s, 123.5 ± 20 imp/s, 130.6 ± 15.3 imp/s, 147.7 ± 17.9 imp/s; for wi/wi: 64.4 ± 13.1 imp/s, 83.6 ± 14.5 imp/s, 99.0 ± 17.3 imp/s, 102.6 ± 21.1 imp/s; wt without glut vs 100 nm, p = 0.026; wt without glut vs 1 μm, p = 0.034; wi/wi without glut vs 100 nm, p = 0.009; wi/wi without glut vs 1 μm, p = 0.045, paired t test). E, Percentage increase in pSN firing in the presence of glutamate, for wild-type (blue) and wi/wi mutant (red) Sol pSNs. Increases in pSN firing are proportionally similar between wild-type and wi/wi mutants (wt vs wi/wi in 10 nm glut, p = 0.39; in 100 nm glut, p = 0.69; in 1 μm glut, p = 0.91; Mann–Whitney rank sum test). C–E, Error bars indicate SEM. Number of Sol muscles analyzed is indicated in parentheses. *p < 0.05, **p < 0.01. n.s., Not significant.