Large fibre size in skeletal muscle is metabolically advantageous.

Skeletal muscle fibre size is highly variable, and while diffusion appears to limit maximal fibre size, there is no paradigm for the control of minimal size. The optimal fibre size hypothesis posits that the reduced surface area to volume in larger fibres reduces the metabolic cost of maintaining the membrane potential, and so fibres attain an optimal size that minimizes metabolic cost while avoiding diffusion limitation. Here we examine changes during hypertrophic fibre growth in metabolic cost and activity of the Na⁺-K⁺-ATPase in white skeletal muscle from crustaceans and fishes. We provide evidence for a major tenet of the optimal fibre size hypothesis by demonstrating that larger fibres are metabolically cheaper to maintain, and the cost of maintaining the membrane potential is proportional to fibre surface area to volume. The influence of surface area to volume on metabolic cost is apparent during growth in 16 species spanning a 20-fold range in fibre size, suggesting that this principle may apply widely.