The Foundation: Skeletal Muscle Physiology

Melissa Jefferson-Wooden of the U.S., Jamaica’s Tina Clayton and Poland’s Ewa Swoboda in action during the Women’s 100m REUTERS/Aleksandra Szmigiel

A clear understanding of skeletal muscle physiology forms the foundation for the treatment, management, and rehabilitation of athletes and physically active individuals. Advances in muscle biology have significantly expanded classical models of muscle function, particularly in areas such as calcium regulation, fiber-type plasticity, and fatigue mechanisms.

While traditional models of skeletal muscle physiology focused primarily on sarcomeric organization and excitation–contraction coupling (ECC), emerging research has broadened our understanding of calcium handling, fiber plasticity, and fatigue mechanisms^(1,2). This review integrates foundational principles of skeletal muscle structure and function with contemporary advances in calcium entry pathways, including store-operated calcium entry (SOCE) and excitation-coupled calcium entry (ECCE).

Introduction

Skeletal muscle accounts for approximately 40% of total body mass and represents 50–75% of total body protein content^(3–5). Beyond enabling voluntary movement, skeletal muscle plays a crucial role in systemic metabolism, including glucose regulation, thermogenesis, and endocrine signaling⁽³⁾.

Understanding the structural and physiological properties of skeletal muscle provides essential insights for clinicians involved in performance training, injury rehabilitation, and neuromuscular disease management.

Structural Organization

Skeletal muscle displays a hierarchical structure that extends from the whole muscle to the molecular components of the sarcomere^(3,4). Each muscle is composed of bundles of muscle fibers, which themselves contain myofibrils, which are composed of repeating contractile units known as sarcomeres.

The sarcomere, bounded by Z-discs, is the fundamental contractile unit of skeletal muscle. Within this structure, thick filaments composed of myosin interact with thin filaments composed primarily of actin, along with regulatory proteins such as tropomyosin and the troponin complex (see figure 1)^(3,4).

“A clear understanding of skeletal muscle physiology forms the foundation...”

These contractile elements are supported by surrounding connective tissue structures, often referred to collectively as myofascia, which provide mechanical scaffolding and contribute to force transmission within the muscle.