Force reduction uncoupled from pH and H2PO 4 − in rat gastrocnemius in vivo with continuous 2-Hz stimulation
The aim of this study was to examine the effect of the products of ATP hydrolysis on the fatigue process in rat gastrocnemius in vivo. Adult male Sprague-Dawley rats (300–400 g) were anesthetized and ventilated in a custom-built cradle fitted with a force transducer that could be placed into a 7-T NMR magnet. The muscle was stimulated continuously at 2 Hz for 20 min ( n = 7). Isometric twitch force increased in the first 4 min of stimulation accompanied by changes in twitch duration (20% increase in relaxation time). Prolonged relaxation was associated with changes in cytosolic pH (6.91 to 6.58), lactate (1.8 to 12.6 μmol/g wet wt), and H2PO[Formula: see text] (7.57 to 13.99 mM). After 4 min, relaxation time, pH, lactate, and H2PO[Formula: see text] returned toward control values as twitch force progressively decreased. No correlation was found between force decline (or twitch broadening) and total phosphate (3 to 23 mM), free [ADP] (18 to 95 μM), free [Mg2+] (0.58 to 0.96 mM), or free energy of ATP hydrolysis (−65 to −55 kJ/mol). We conclude that force decline is not due to increased pH and/or H2PO[Formula: see text] but to fatigue of the fast-twitch fibers, possibly linked to glycogen depletion and/or failure of nerve impulse transmission in these fibers.