Endplate blocking actions of lophotoxin.
Effects of lophotoxin (LTX), a neurotoxin isolated from Pacific sea whips Lophogorgia rigida and Lophogorgia chelensis, on neuromuscular transmission were assessed in the rat phrenic nerve-hemidiaphragm preparation using conventional microelectrode recording techniques, and in the frog cutaneous pectoris preparation using two microelectrode voltage clamp techniques. LTX (2-25 microM) produced a progressive, irreversible block of miniature endplate potential (m.e.p.p.) and endplate potential (e.p.p.) amplitude. M.e.p.p. amplitude histograms were shifted markedly in the direction of lower amplitude by LTX. These effects occurred following a latency of 25-40 min. The latency to onset of block was decreased with increasing LTX concentrations. In some preparations, LTX produced a transient increase in m.e.p.p. frequency during the first 5 min of application; however, m.e.p.p. frequency then declined to complete block. The depressant effect of LTX on m.e.p.p. and e.p.p. amplitude progressed to complete block irrespective of the LTX concentration. LTX also blocked the endplate depolarization produced by iontophoretic application of acetylcholine (ACh). The resting membrane potential of skeletal muscle fibres was unaffected by LTX. In voltage clamp experiments, LTX (15 microM) depressed the peak amplitude of the endplate current (e.p.c.) nearly uniformly at potentials between -120 and +60 mV. LTX did not affect the e.p.c. reversal potential or the kinetics of e.p.c. decay suggesting that LTX does not block open ACh channels. E.p.c. block by LTX was also progressive and irreversible. The results indicate that LTX blocks neuromuscular transmission by a postjunctional action. The binding site of LTX may be different from that of ACh.
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003064:Cnidarian Venoms / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D066298:In Vitro Techniques; D007478:Iontophoresis; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009045:Motor Endplate / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D011894:Rana pipiens; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D013729:Terpenes
D003064:Cnidarian Venoms; D004224:Diterpenes; D011950:Receptors, Cholinergic; D013729:Terpenes; C030303:lophotoxin; D000109:Acetylcholine