Enhancement by Anemonia sulcata toxin II of spontaneous quantal transmitter release from mammalian motor nerve terminals.
The action of Anemonia sulcata toxin II (ATX-II) on spontaneous quantal transmitter release from motor nerve terminals was investigated by recording miniature end-plate potentials (MEPPs) from isolated mouse phrenic nerve--hemidiaphragm nerve--muscle preparations. ATX-II (3.2 microM) when applied for 3-40 min to junctions bathed in a normal ionic medium enhanced about one hundred fold the rate of spontaneous MEPPs. Concomitantly, ATX-II depolarized the muscle fiber. The effect of the toxin on MEPP frequency was markedly reduced when junctions were exposed to Na-deficient solutions or pre-treated with dantrolene sodium (10 microM). ATX-II (0.24-3.2 microM) increased MEPP rate in junctions exposed to a Ca-free medium containing 2 mM EGTA and 2 mM Mg2+ in a dose- and time-dependent manner. Tetrodotoxin (0.2-1 microM) prevented the effects of ATX-II on MEPP frequency and on the resting membrane potential of muscle fibers. Tetrodotoxin also antagonized the acceleration of MEPP induced by ATX-II. The experimental findings suggest that ATX-II acts to increase quantal transmitter output from motor nerve terminals by enhancing Na+ influx through tetrodotoxin-sensitive presynaptic channels, since ATX-II action does not appear to depend upon entry of Ca2+ from the extracellular medium. It is likely that ATX-II, by increasing intraterminal Na+ concentration, may trigger calcium release from internal stores.
Molgo
J
J
Lemeignan
M
M
Tazieff-Depierre
F
F
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D003064:Cnidarian Venoms / Q000494:pharmacology*; D003620:Dantrolene / Q000494:pharmacology; D003964:Diaphragm / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010791:Phrenic Nerve; D012964:Sodium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D003064:Cnidarian Venoms; D018377:Neurotransmitter Agents; D013779:Tetrodotoxin; C028800:toxin II (Anemonia sulcata); D012964:Sodium; D003620:Dantrolene; D002118:Calcium