Estimates of persistent inward currents in lower limb motoneurons are larger in females than in males

Noninvasive recordings of motor unit (MU) spike trains help us understand how the nervous system controls movement and how it adapts to various physiological conditions. The majority of participants in human and nonhuman animal physiology studies are male, and it is assumed that mechanisms uncovered in these studies are shared between males and females. However, sex differences in neurological impairment and physical performance warrant the study of sex as a biological variable in human physiology and perform- ance. To begin addressing this gap in the study of biophysical properties of human motoneurons, we quantified MU discharge rates and estimates of persistent inward current (PIC) magnitude in both sexes. We decomposed MU spike trains from the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (SOL) using high-density surface electromyography and blind source separation algo- rithms. Ten participants of each sex performed slow triangular (10 s up and down) isometric contractions to a peak of 30% of their maximum voluntary contraction. We then used linear mixed-effects models to determine if peak discharge rate and estimates of PICs were predicted by the fixed effects of sex, muscle, and their interaction. Despite a lack of sex-differences in peak discharge rates across all muscles, estimates of PICs were larger [v2(1)=6.26, P=0.012] in females [4.73 +/- 0.242 pulses per second (pps)] than in males (3.81 +/- 0.240 pps). These findings suggest that neuromodulatory drive, inhibitory input, and/or biophysical properties of moto- neurons differ between the sexes and may contribute to differences in MU discharge patterns. NEW & NOTEWORTHY Sex-related differences in motoneuron analyses have emerged with greater inclusion of female partici- pants, however, mechanisms for these differences remain unclear. Estimates of persistent inward currents (i.e., DF) in motoneur- ons of the lower limb muscles were larger in females than in males. This suggests neuromodulatory drive, monoaminergic signaling, intrinsic motoneuron properties, and/or descending motor commands may differ between the sexes, which provides a potential mechanism underlying previously reported sex-related differences in motoneuron discharge patterns.