The interactive effects of biological sex and skeletal muscle fiber properties on knee-extensor muscle relaxation induced by TMS in unfatigued and fatigued states

Purpose: Biological sex and muscle fiber type affect muscle relaxation. However, assessments probing the interaction effect are lacking. This study examined whether any difference in transcranial magnetic stimulation (TMS)-induced muscle relaxation results from the interaction effects of biological sex and skeletal muscle fiber properties in (un)fatigued knee extensors. Methods: TMS-induced muscle relaxation was assessed in twenty participants (10 females/10 males) before, after a 2-min sustained maximum voluntary isometric contraction, and four times within 8-min of recovery. Vastus lateralis muscle tissue was obtained separately from the participants' dominant limb. Results: Type I fiber distribution was not different between sexes (females: 53 ± 11%; males: 43 ± 9%; P = 0.050), and relative cross-sectional area of type I fibers was larger for females (53 ± 3% vs. 48 ± 4%; P = 0.005). Females exhibited ~ 40% slower muscle relaxation in an unfatigued state (-8.8 ± 2.3 s- 1 vs. -12.4 ± 1.9 s- 1; P < 0.001), and ~ 21% smaller relative decline with fatigue (females: 69 ± 26% of pre-exercise; males: 48 ± 14% of pre-exercise; P = 0.013). The relative slowing of muscle relaxation with fatigue remained lower in females through 8 min post-exercise (females: 125 ± 26% of pre-exercise; males: 101 ± 8% of pre-exercise; P = 0.009). Only in females was the relative cross-sectional area of type I fibers correlated with muscle relaxation at baseline (r = 0.82, adjusted P = 0.018), fatigue index (r = 0.78, adjusted P = 0.032), and recovery index (r = 0.89, adjusted P = 0.007). Conclusions: Among females, muscle fiber characteristics were associated with TMS-induced muscle relaxation, whereas no comparable associations were observed in males. This underscores the importance of considering biological sex and skeletal muscle fiber properties when assessing changes in muscle relaxation responses to exercise.