ELECTRICAL-STIMULATION INACTIVATES MUSCLE ACETYL-COA CARBOXYLASE AND INCREASES AMP-ACTIVATED PROTEIN-KINASE

Muscle malonyl-CoA decreases during exercise or electrical stimulation , the exercise-induced decline being accompanied by changes in the kin etic properties [maximal velocity (V-max), activation constant (K-a), and citrate concentration required to produce 50% V-max (K-0.5)] of ac etyl-CoA carboxylase (ACC) and by an increase in the AMP-activated pro tein kinase activity (AMPK). This study was designed to ascertain whet her the exercise-induced changes are contraction mediated and, if so, to follow the time course of these changes. The left sciatic nerve of rats was stimulated at 1 Hz for 0, 2, 5, 10, 20, or 30 min, and the ga strocnemius-plantaris muscle group was then excised, frozen in liquid nitrogen, and later analyzed for malonyl-CoA and other metabolites. AC C and AMPK activities were quantitated in ammonium sulfate precipitate s from homogenates prepared from the frozen muscles. The V-max and K-a of ACC for citrate decreased and increased, respectively, over the fi rst 10 min of stimulation, but significantly increased AMPK activity w as not observed until 10 to 20 min of stimulation (P < 0.05). Stimulat ion increased estimated free AMP (P < 0.05). Thus exercise-induced cha nges in functional properties of ACC appear to be contraction mediated and are accompanied by increased AMPK activity and an increase in the estimated free AMP.