Johanna Flodin¹ ² | Stefan M. Reitzner³ ⁴ | Eric B. Emanuelsson³ | Carl Johan Sundberg³ ⁵ ⁶ | Paul Ackermann ¹ ²

¹Integrative Orthopedic Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

²Department of Trauma, Acute Surgery and Orthopedics, Karolinska University Hospital, Stockholm, Sweden

³Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

⁴Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden

⁵Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden

⁶Department of Laboratory Medicine, Division of Clinical Physiology, Karolinska Institutet, Huddinge, Sweden

Abstract

Aim: The influence on acute skeletal muscle transcriptomics of neuromuscular electrical stimulation (NMES), as compared to established exercises, is poorly understood. We aimed to investigate the effects on global mRNA expression in the quadriceps muscle early after a single NMES-session, compared to the effects of voluntary knee extension exercise (EX), and to explore the discomfort level.

Methods: Global vastus lateralis muscle gene expression was assessed (RNA-

sequencing) in 30 healthy participants, before and 3h after a 30-min session of NMES and/or EX. The NMES-treatment was applied using textile electrodes integrated in pants and set to 20% of each participant's pre-tested MVC mean (±SD) 200 (±80) Nm. Discomfort was assessed using Visual Analogue Scale (VAS, 0–10). The EX-protocol was performed at 80% of 1-repetition-maximum.

Results: NMES at 20% of MVC resulted in VAS below 4 and induced 4448 dif-

ferentially expressed genes (DEGs) with 80%-overlap of the 2571 DEGs of EX. Genes well-known to be up-regulated following exercise, for example, PPARGC1A, ABRA, VEGFA, and GDNF, were also up-regulated by NMES. Gene set enrichment analysis demonstrated many common pathways after EX and NMES. Also, some pathways were exclusive to either EX, for example, muscle tissue proliferation, or to NMES, for example, neurite outgrowth and connective tissue proliferation.

Conclusion: A 30-min NMES-session at 20% of MVC with NMES-pants, which can be applied with an acceptable level of discomfort, induces over 4000 DEGs, of which 80%-overlap with DEGs of EX. NMES can induce exercise-like molecular effects, that potentially can lead to health and performance benefits in individuals who are unable to perform resistance exercise.

KEYWORDS

electrical stimulation therapy, gene expression, muscle stimulation, resistance exercise, RNA sequencing, skeletal muscles, smart textiles

How to cite this article:  Flodin J, Reitzner SM, Emanuelsson EB, Sundberg CJ, Ackermann P. The effect of neuromuscular electrical stimulation on the human skeletal muscle transcriptome. Acta Physiol. 2024;00:e14129. doi:10.1111/apha.14129

EXCERPT FROM THE STUDY REGARDING THE KNEE EXTENSOR FORCE MEASUREMENTS

“The participants isometric knee extension torque was measured using an isokinetic dynamometer (Biodex System 3 Pro; Biodex Medical Systems, Shirley, New York) with the knee joint in 90 degrees of flexion and position as describe in a previous study.1 The knee extension torque was additionally measured using the EasyForce dynamometer (Meloq AB, Stockholm, Sweden) to enable a constant supervision of the produced force during the biopsy session and ensure that the targeted 20% of MVC was reached during NMES. Correlation analyses demonstrated good reliability of the measurements with the EasyForce and Biodex, for both the MVC (R2 = 0.76) and 20% of MVC (R2 = 0.70) (Figure S1).

Thereafter, the single-leg 1 repetition maximum (1RM) was measured in a knee extension machine according to a standardized protocol. The measurement was performed after a warm-up of eight repetitions of approximately 50% of MVC, followed by tree repetition at an estimated 80% of MVC. Thereafter each participant got three attempts to reach the 1RM with 1 min rest in between. The mean (SD) values for the MVC determined with the Biodex and EasyForce dynamometers for the leg randomized to NMES, and the 1RM for the leg randomized to EX are presented in Table 1.”

1) Flodin J, Mikkelsen C, Ackermann PW. Knee extensor force production and discomfort during neuromuscular electrical stimulation of quadriceps with and without gluteal muscle co-stimulation. Eur J Appl Physiol. 2022; 122: 1521-1530. doi:10.1007/s00421-022-04949-9

Read the interview with the researcher Dr. Stefan Markus Reitzner: Interview