Inorganic phosphate speeds loaded shortening in rat skinned cardiac myocytes

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Abstract
Force generation in striated muscle is coupled with inorganic phosphate (Pi) release from myosin, because force falls with increasing Pi concentration ([Pi]). However, it is unclear which steps in the cross-bridge cycle limit loaded shortening and power output. We examined the role of Pi in determining force, unloaded and loaded shortening, power output, and rate of force development in rat skinned cardiac myocytes to discern which step in the cross-bridge cycle limits loaded shortening. Myocytes ( n = 6) were attached between a force transducer and position motor, and contractile properties were measured over a range of loads during maximal Ca2+ activation. Addition of 5 mM Pi had no effect on maximal unloaded shortening velocity ( Vo) (control 1.83 ± 0.75, 5 mM added Pi 1.75 ± 0.58 muscle lengths/s; n = 6). Conversely, addition of 2.5, 5, and 10 mM Pi progressively decreased force but resulted in faster loaded shortening and greater power output (when normalized for the decrease in force) at all loads greater than ∼10% isometric force. Peak normalized power output increased 16% with 2.5 mM added Pi and further increased to a plateau of ∼35% with 5 and 10 mM added Pi. Interestingly, the rate constant of force redevelopment ( ktr) progressively increased from 0 to 10 mM added Pi, with ktr ∼360% greater at 10 mM than at 0 mM added Pi. Overall, these results suggest that the Pi release step in the cross-bridge cycle is rate limiting for determining shortening velocity and power output at intermediate and high relative loads in cardiac myocytes.