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  • Title: Differential actions of brevetoxin on phrenic nerve and diaphragm muscle in the rat.
    Author: Deshpande SS, Adler M, Sheridan RE.
    Journal: Toxicon; 1993 Apr; 31(4):459-70. PubMed ID: 8503134.
    Abstract:
    The mechanism of inhibition of skeletal muscle function by brevetoxin (PbTX-3) was examined in vitro in the rat phrenic nerve-diaphragm preparation. PbTX-3 in low concentrations (< 0.06 microM) preferentially blocked conduction in the phrenic nerve without altering the resting membrane potential of the muscle fibers. Endplate potential failure occurred in an all-or-none fashion in the presence of PbTX-3 (> 0.06 microM). An increase in the frequency of miniature endplate potentials resulting from nerve terminal depolarization was observed only after endplate potential failure. Higher concentrations of toxin (> 0.3 microM) depressed directly-elicited muscle twitches and produced significant muscle membrane depolarization. Tetrodotoxin was effective in reversing membrane depolarization and alterations in MEPP frequency caused by PbTX-3. These findings suggest that diaphragmatic failure in PbTX-3 is primarily caused by a block of impulse conduction in the phrenic nerve due to a higher sensitivity of nerve than muscle membrane to the toxin.
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