The effects of biological sex on estimates of persistent inward currents in the human lower limb

Abstract

Non-invasive recordings of motor unit (MU) spike trains help us understand how neural drive is modulated by various motor commands and/or physiological conditions. The majority of study participants in human and non-human animal physiology studies are male, and it is assumed 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 performance. 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 by quantifying ΔF. 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 algorithms. Ten participants of each sex performed slow triangular (10s 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 ΔF were predicted by the fixed effects of sex, muscle, and their interaction. Despite similar peak discharge rates across all muscles, ΔF was larger (χ2(1) = 6.26, p = 0.012) in females (4.73 [0.242 pps]) than males (3.81 [0.240 pps]). These findings suggest that neuromodulatory drive and/or biophysical properties of motoneurons differ between the sexes and may contribute to differences in MU discharge patterns.

Common synaptic inputs and persistent inward currents of vastus lateralis motor units are reduced in older age

“…The reduced PICs in older participants here may be a result of increased inhibitory input levels. Furthermore, the sex-based differences of PIC magnitude recently observed (Jenz et al, 2023) may be explained by hormonal differences which influences 5-HT, that may similarly differ between young and older males.…”

Estimates of persistent inward currents in lower limb muscles are not different between inactive, resistance-trained, and endurance-trained young males

“…It should also be emphasised that results are limited to healthy young males in lower limb muscles, and thus cannot be generalized to other limbs or populations, such as females and the elderly who may exhibit different PIC activity, as found in previous studies (21,33).…”

“…We only recruited males for this study because our attempts to decompose MUs in females were unsuccessful. Factors like subcutaneous fat or the distance between the muscle and the surface array are likely contributors to the lower MU yield in females (21). Participants were required to report no lower limb injuries in the preceding 6 months.…”

Estimates of persistent inward currents in lower limb muscles are not different between inactive, resistance-trained and endurance-trained young individuals

“…It should also be emphasised that results are limited to healthy young males in lower limb muscles, and thus cannot be generalized to other limbs nor populations, such as female and the elderly who may exhibit different PIC activity, as found in previous studies (Orssatto, Borg et al, 2021;Jenz et al, 2023).…”

“…It may be noted that the absence of differences in MU peak discharge rate does not necessarily imply an absence of differences in ΔF. For example, estimates of PICs can be larger in females compared to males despite a lack of sex-differences in peak discharge rates (Jenz et al, 2023). Since PICs significantly alter the intrinsic excitability of motoneurons (Heckman et al, 2009), an increase in PIC magnitude could represent a potential efficient adaptation that would allow for the generation of similar MU outputs with reduced descending ionotropic inputs.…”