TheCa 2+ -ATPaseof skeletalmuscle sarcoplasmic reticulum (SERCA), an integral membrane protein, becomes irre-versibly inactivatedin vitroby the addition of a single bolus of 200–300lM, and this results in a large decrease of theATP-dependentCa 2+ gradient across the sarcoplasmic reticulum (SR) membranes. The inactiva-tion of SERCA is raised by treatment of SR vesicles with repetitivemicromolar pulses of peroxynitrite.