Effects of (+)-tubocurarine on neuromuscular facilitation and depression in rat diaphragm

Effects of (+)-tubocurarine on neuromusclular facilitation and depression were studied in the rat phrenic nerve-diaphragm. The paired end-plate potential (EPP) method of analysis was used. Tubocurarine caused a significant decrease in the EPP 2/EPP 1 ratio of EPP pairs elicited at a stimulus interval of 20 msec in the cut muscle preparation. Studies of tubocurarine with respect to the equilibrium potential of EPP 1 and EPP 2 and iontophoretic acetylcholine potential pairs, indicated that the effect of tubocurarine on the EPP ratio was not associated with a postsynaptic action of tubocurarine. Furthermore, tubocurarine did not alter the amplitude ratio of the nerve terminal action potentials. The effects of tubocurarine on the EPP 2/EPP 1 ratio at various stimulus intervals were studied in the cut muscle preparation. In the control condition, facilitation (EPP 2/EPP 1 ratio > 1.01 occurred at 5 and 10 msec stimulus intervals; depression (EPP 2/EPP 1 ratio < 1.0) occurred at longer stimulus intervals. Tubocurarine significantly decreased the EPP ratio at stimulus intervals of 10 100 msec. In the low Ca 2+/high Mg 2+ Krebs solution, only facilitation occurred and under these conditions tubocurarine did not decrease the EPP 2/EPP 1 ratio. These results indicate that tubocurarine preferentially enhances depression and that facilitation is relatively unaffected by tubocurarine. Altogether, the results are consistent with the notion that, in addition to its postsynaptic actions, tubocurarine affects acetylcholine storage and release in the nerve terminal.