Release of creatine kinase and lactate dehydrogenase from frog skeletal muscles treated with imipramine

Frog sartorius and extensor longus digiti IV ("toe") muscles were mounted in sample collecting units, isometric tension was recorded and the activities of creatine kinase and lactate dehydrogenase released into the bathing medium were measured. Addition of imipramine (greater than 0.2 mM) to the control medium induced muscle contractures and increased the rates of enzyme release. Electronmicrographs of muscles exposed to imipramine (0.5--1.0 mM) showed fibers in which the extracellular marked horseradish peroxidase was detected in the sarcoplasm. Both the enzyme-releasing and the contractile effects of imipramine were inhibited by procaine (but not by lidocaine) and were enhanced by replacement of external chloride ions with propionate. The data are consistent with the suggestion that events associated with tension development contribute greatly to the imipramine-induced loss of sarcoplasmic enzymes from frog skeletal muscles. The elevated Ca++ concentration in the sarcoplasm during the imipramine-induced contracture is thought to lead to changes in the plasma membrane that account for the increased enzyme loss and for the penetration of horseradish peroxidase into the sarcoplasm.