The force-calcium relationship is not affected by the cross-sectional area of skinned muscle fibres from rat soleus.

Abstract

Proportionality between force and muscle cross-sectional area (CSA) is a foundational principle in muscle mechanics. However, CSA-normalized force (known as specific force) is often lower in fibres with large CSAs compared to fibres with small CSAs from the same sample population. Many physiological mechanisms proposed to account for CSA-dependence of specific force converge on the requirement for fibre CSA to impact the relationship between force and the concentration of force-activating calcium. To determine if features of the force-calcium relationship exhibited CSA-dependence in mammalian skinned muscle fibres, force-calcium relationships were generated for 85 skinned slow soleus fibres of male Sprague-Dawley rats (n = 54 rats, 1-5 fibres per rat, age = 24 weeks, experimental temperature = 18 °C) and fit using the Hill equation. Fibres were separated into quartiles based on their CSA and then compared. Despite specific force being 46 % higher (P < 0.01) in the smallest (160 ± 51 mN∙mm^-2; CSA = 3649 ± 708 μm²) compared to the largest (110 ± 20 mN∙mm^-2; CSA = 8671 ± 1319 μm²) quartile, neither the calcium-sensitivity of force production (pCa50; P = 0.47; F(dFn = 3,DFd = 81) = 0.86) nor the Hill coefficient (n_H; P = 0.38; F(dFn = 3,DFd = 81) = 1.03) differed significantly between quartiles (smallest quartile: pCa50 = 6.015 ± 0.097, n_H = 1.80 ± 0.69; largest quartile: pCa50 = 6.062 ± 0.097, n_H = 1.63 ± 0.32). Force plateaus were observed at higher calcium concentrations in all fibres indicating that calcium was adequate for full activation. These findings add to the body of evidence suggesting that CSA-dependence of specific force in mammalian skinned fibres is an artifact attributable to the considerable imprecision associated with the assessment of fibre CSA, and not a physiological phenomenon which would require consideration when modeling muscle force output.