Inactivation of sarcoplasmic reticulum Ca(2+)-atpase in low-frequency stimulated rat muscle.

Continuous low-frequency stimulation (CLFS) by implanted electrodes for 12-24 h led to a significant (approximately 30%) decrease in the activity of sarcoplasmic reticulum Ca(2+)-ATPase in fast-twitch extensor digitorum longus (EDL) and tibialis anterior (TA) muscles of intact rats. The decline in catalytic activity after 24 h of CLFS was accompanied by an approximately twofold increase in dinitrophenylhydrazine-reactive carbonyl groups of the enzyme. It also correlated with an immunochemically determined 30% decrease in Ca2(+)-ATPase protein. Recovery studies after 12 h of CLFS revealed a relatively slow (48-72 h) re-establishment of normal catalytic activity. These findings suggest that the 30% decline of Ca(2+)-ATPase activity in low-frequency stimulated rat muscle led to an irreversible modification by protein oxidation. The decrease in Ca(2+)-ATPase protein most likely resulted from the degradation of inactive Ca(2+)-ATPase molecules. The relatively slow recovery of Ca(2+)-ATPase activity suggests that de novo synthesis of the enzyme may be necessary to re-attain normal activity.