Inactivation of sarcoplasmic reticulum Ca²⁺-ATPase in low-frequency stimulated rat muscle

Abstract

Continuous low-frequency stimulation (CLFS) by implanted electrodes for 12–24 h led to a significant (∼30%) decrease in the activity of sarcoplasmic reticulum Ca²⁺-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 Ca²⁺-ATPase activity in low-frequency stimulated rat muscle led to an irreversible modification by protein oxidation. The decrease in Ca²⁺-ATPase protein most likely resulted from the degradation of inactive Ca²⁺-ATPase molecules. The relatively slow recovery of Ca²⁺-ATPase activity suggests that de novo synthesis of the enzyme may be necessary to re-attain normal activity.