Effects of ADP on sarcoplasmic reticulum function in mechanically skinned skeletal muscle fibres of the rat

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Abstract
The sarcoplasmic reticulum (SR) Ca2+ content (expressed in terms of endogenous SR Ca2+ content under physiologically resting conditions and measured from caffeine-induced force responses) and the effective rates of the SR Ca2+ pump and SR Ca2+ leak (measured from the temporal changes in SR Ca2+ content) were determined in mechanically skinned skeletal muscle fibres of the rat at different [ADP] (< 0.10 μm to 1.04 mm). The estimated SR Ca2+ pump rate at 200 nm Ca2+ did not change when [ADP] increased from below 0.10 μm to 10 μm but decreased by about 30 % when [ADP] increased from 10 μm to 1.04 mm. The rate constant of SR Ca2+ leak increased markedly with rising [ADP] when [Ca2+] in solution was 200 nm (apparent dissociation constant KdADP= 64 ± 27 μm). Decreasing the [Ca2+] in solution from 200 nm to < 10 nm significantly increased the leak rate constant at all [ADP]. The SR Ca2+ leak rate constant could be significantly reduced by blocking the SR Ca2+ pump with 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ). The decrease in the SR Ca2+ pump rate and the increase in the rate constant of SR Ca2+ leak when the [ADP] increased from < 0.10 μm to 1.04 mm caused a 4.4-fold decrease in SR Ca2+ loading ability at 200 nm Ca2+. The results can be fully explained by a mechanism whereby the presence of ADP causes a marked increase in the ADP-sensitive fraction of the phosphorylated pump protein, which can act as a Ca2+-Ca2+ exchanger and demonstrates that ADP is an important modulator of SR function in skeletal muscle.