Nerve electrical activity; depression by puromycin not related to inhibited protein synthesis

Puromycin (1 mM) causes a reversible decrease in spike potential and positive after potential amplitudes of rabbit vagus nerve in vitro . This failure is independent of the rate of stimulation in contrast to the failure following sodium pump inhibition by ouabain. Puromycin does not inhibit brain Na‐K ATPase in vitro . There is no reduction in the action potential by either of the protein synthesis inhibitors, chloramphenicol or cycloheximide. Puromycin inhibits even in the presence of cycloheximide, a compound which blocks the release of abnormal polypeptides by puromycin. Puromycin aminonucleoside does not have the puromycin effect nor does dibutyryl‐cyclic‐3′,5′‐AMP protect the nerve against puromycin. Puromycin can inhibit ribosomal protein synthesis and interfere with purine metabolism but these actions do not appear to be the basis of the action potential decrease. A more likely site of action is interference with glycolipid and glycoprotein formation or a direct effect on the membrane. It is concluded that neither mitochondrial nor ribosomal protein synthesis is critical to the short term maintenance of the action potential.