Leptinotarsin-D, a neurotoxic protein, evokes neurotransmitter release from, and calcium flux into, isolated electric organ nerve terminals.
Previous work has demonstrated that the neurotoxin leptinotarsin elicits release of neurotransmitter from mammalian nerve terminals, and it has been suggested that the toxin may act either as a direct agonist of voltage-sensitive calcium channels in these terminals (Crosland et al., 1984) or as a calcium ionophore (Madeddu et al., 1985a,b). Preliminary studies (Yeager et al., 1987) demonstrated that leptinotarsin also evokes transmitter release from isolated elasmobranch electric organ nerve terminals. We now report further investigations of the effects of leptinotarsin in this system. The action of the toxin is saturable, releasing about the same small fraction of total transmitter as that released by depolarization. An upper limit for the concentration for half maximal release is estimated to be 4 nM. Leptinotarsin-evoked transmitter release exhibits behavior very similar to depolarization-evoked release with respect to dependence on Ca2+, Ba2+, and Sr2+ and blockade by Co2+, Cd2+, and trifluoperazine. Leptinotarsin also promotes the uptake of calcium into synaptosomes to a degree similar to that caused by depolarization by K+. The binding of leptinotarsin to nerve terminals is probably Ca2+ dependent and receptor mediated. Taken together with the behavior of leptinotarsin-evoked release in other preparations, these results are consistent with the hypothesis that this toxin acts by opening a presynaptic calcium channel. However, the possibility that leptinotarsin is a calcium ionophore cannot be excluded.
Miljanich
G P
GP
Department of Biology, University of Southern California, Los Angeles 90089-0371.
Yeager
R E
RE
Hsiao
T H
TH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004557:Electric Organ / Q000187:drug effects / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects; D019476:Insect Proteins; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D019476:Insect Proteins; D007473:Ion Channels; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D011506:Proteins; C023401:leptinotarsin protein, Leptinotarsa haldemani; D000255:Adenosine Triphosphate; D002118:Calcium