DIFFERENTIAL ACTIONS OF BREVETOXIN ON PHRENIC-NERVE AND DIAPHRAGM MUSCLE IN THE RAT

The mechanism of inhibition of skeletal muscle function by brevetoxin (PbTX-3) was examined in vitro in the rat phrenic nerve-diaphragm prep aration. PbTX-3 in low concentrations ( < 0.06 muM) preferentially blo cked conduction in the phrenic nerve without altering the resting memb rane potential of the muscle fibers. Endplate potential failure occurr ed in an all-or-none fashion in the presence of PbTX-3 ( > 0.06 muM). An increase in the frequency of miniature endplate potentials resultin g from nerve terminal depolarization was observed only after endplate potential failure. Higher concentrations of toxin ( > 0.3 muM) depress ed directly-elicited muscle twitches and produced significant muscle m embrane depolarization. Tetrodotoxin was effective in reversing membra ne depolarization and alterations in MEPP frequency caused by PbTX-3. These findings suggest that diaphragmatic failure in PbTX-3 is primari ly caused by a block of impulse conduction in the phrenic nerve due to a higher sensitivity of nerve than muscle membrane to the toxin.