[The effect of a p-phenylenediamine containing hair dye on the Ca2+ mobilization in the chemically skinned skeletal muscle of the rat]

Abstract

In order to clarify the mechanism of a p-phenylenediamine (PPD)-related occurrence of rhabdomyolysis, the pharmacological effects of PPD, a main component of hair dyes, on the function of the contractile proteins and the sarcoplasmic reticulum (SR) have been investigated in single skeletal muscle fibers of the rat by using the skinned fiber method. The results of our findings are enumerated below 1) A positive contraction of the skinned fibers by the PPD, and a complete suppression of the contraction by Mg2+, and a negative contraction by caffeine while under conditions with 50 mM of PPD were noted, suggesting that the contraction of the muscle by PPD is caused by the release of Ca2+ from the SR. 2) PPD inhibited the Ca2+ uptake by the SR in a concentration-dependent manner. 3) PPD greatly accelerated Ca2+ leakage from the SR, and the number of Ca2+ remnants 3 minutes after the administration of 50 mM of PPD amounted to only 3%. 4) The calcium-induced calcium release (CICR) was accelerated in areas with a low Ca2+ concentration, and the amount of Ca2+ released at a pCa of 7.5 showed an increase of up to 63% on PPD administration of 50 mM. 5) PPD did not influence the Ca2+ sensitivity of the contractile system. It thus has been speculated that PPD can bring about rhabdomyolysis by promoting the CICR and leakage of Ca2+ from the SR, this being followed by an increase in the Ca2+ concentration and by consequent changes that develop in the muscle, such as continuous contraction, an irreversible change in the muscle's structure and/or a hypermetabolic change.