α-Latrocrustatoxin Increases Neurotransmitter Release by Activating a Calcium Influx Pathway at Crayfish Neuromuscular Junction

Author:

Elrick Donald B.1,Charlton Milton P.1

Affiliation:

1. Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada

Abstract

α-latrocrustatoxin (α-LCTX), a component of black widow spider venom (BWSV), produced a 50-fold increase in the frequency of spontaneously occurring miniature excitatory postsynaptic potentials (mEPSPs) at crayfish neuromuscular junctions but did not alter their amplitude distribution. During toxin action, periods of high-frequency mEPSP discharge were punctuated by periods in which mEPSP frequency returned toward control levels. EPSPs were increased in amplitude during periods of enhanced mEPSP discharge. α-LCTX had no effect when applied in Ca2+-free saline, but subsequent addition of Ca2+ caused an immediate enhancement of mEPSP frequency even when α-LCTX was previously washed out of the bath with Ca2+-free saline. Furthermore removal of Ca2+from the saline after α-LCTX had elicited an effect immediately blocked the action on mEPSP frequency. Thus α-LCTX binding is insensitive to Ca2+, but toxin action requires extracellular Ca2+ ions. Preincubation with wheat germ agglutinin prevented the effect of α-LCTX but not its binding. These binding characteristics suggest that the toxin may bind to a crustacean homologue of latrophilin/calcium-independent receptor for latrotoxin, a G-protein-coupled receptor for α-latrotoxin (α-LTX) found in vertebrates. α-LCTX caused “prefacilitation” of EPSP amplitudes, i.e., the first EPSP in a train was enhanced in amplitude to a greater degree than subsequent EPSPs. A similar alteration in the pattern of facilitation was observed after application of the Ca2+ionophore, A23187, indicating that influx of Ca2+ may mediate the action of α-LCTX. In nerve terminals filled with the Ca2+ indicator, calcium green 1, α-LCTX caused increases in the fluorescence of the indicator that lasted for several minutes before returning to rest. Neither fluorescence changes nor toxin action on mEPSP frequency were affected by the Ca2+ channel blockers ω-agatoxin IVA or Cd2+, demonstrating that Ca2+ influx does not occur via Ca2+ channels normally coupled to transmitter release in this preparation. The actions of α-LCTX could be reduced dramatically by intracellular application of the Ca2+ chelator, bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid. We conclude that induction of extracellular Ca2+influx into nerve terminals is sufficient to explain the action of α-LCTX on both spontaneous and evoked transmitter release at crayfish neuromuscular junctions.

Publisher

American Physiological Society

Subject

Physiology,General Neuroscience

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