The effects of inorganic phosphate on contractile function of slow skeletal muscle fibres are length-dependent

Muscle operates across a wide range of sarcomere lengths. Inorganic phosphate (P_i) diminishes force output of striated muscle, with greater influence at short relative to long sarcomere lengths in fast skeletal and cardiac muscle fibres. The purpose of this study was to fill a gap in the literature regarding the length-dependent effects of P_i on contractile function of slow skeletal muscle fibres. Permeabilized slow skeletal muscle fibres from rabbit soleus were assessed at average sarcomere lengths of 2.0, 2.4, or 2.8 μm, with and without 20 mM P_i added to activating solutions (22±1 °C). The magnitude of P_i-induced reductions in peak force (43 ± 7% at 2.0 μm, 38 ± 7% at 2.4 μm, and 31 ± 8% at 2.8 μm) and peak stiffness (41 ± 9% at 2.0 μm, 36 ± 8% at 2.4 μm, and 26 ± 9% at 2.8 μm) were length dependent. Peak stiffness was less affected by P_i than peak force. P_i diminished the Ca²⁺-sensitivity of the force-pCa and stiffness-pCa relationships to a greater extent at 2.8 μm than 2.0 μm. Comparable results were obtained from a cooperative model of Ca²⁺ and myosin binding to regulated actin. In conclusion, P_i is more detrimental to the peak force output of slow skeletal muscle fibres held at short relative to long sarcomere lengths, whereas P_i has a greater effect on the Ca²⁺-sensitivity of force production at long relative to short sarcomere lengths. Stiffness data suggest that P_i-induced reductions in force are primarily due to fewer bound cross-bridges, with a lesser contribution attributable to lower average force per cross-bridge.