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 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.
Neurotoxicology Branch, USAMRICD, Aberdeen Proving Ground, MD 21010-5425.
S S
SS
Deshpande
M
M
Adler
R E
RE
Sheridan
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003964:Diaphragm / Q000187:drug effects; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D008387:Marine Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000633:toxicity; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D035964:Oxocins; D010791:Phrenic Nerve / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012132:Respiratory Muscles / Q000187:drug effects*; D000095702:Polyether Toxins
D008387:Marine Toxins; D009467:Neuromuscular Depolarizing Agents; D009498:Neurotoxins; D035964:Oxocins; C053342:brevetoxin; D000095702:Polyether Toxins