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Journal of Neuroscience, Vol 1, 259-270, Copyright © 1981 by Society for Neuroscience
ARTICLE
Snake alpha-toxin effects on cholinergic and noncholinergic responses of Aplysia californica neurons
JK Ono and PM Salvaterra
The effects of alpha-toxins from Bungarus multicinctus (alpha BuTX) and Naja naja siamensis (alpha NTX) were studied on synaptic responses and on extrasynaptic responses to focally applied acetylcholine (ACh), histamine (Hm), gamma-aminobutyric acid (GABA), and glutamate (glu) in neurons of the marine mollusc, Aplysia californica. Binding of 125I- alpha BuTX to Aplysia ganglia homogenates was pharmacologically characterized and compared with the pharmacological sensitivity of 125I- alpha BuTX binding to rat brain membrane preparations. Both alpha BuTX and alpha NTX at 10(-5) M reversibly inhibited the ACh-induced increase in Cl- conductance (GCl) without affecting ACh responses mediated by an increase in Na+ conductance (GNa) or an increase in K+ conductance (GK). In addition, both alpha-toxin reversibly inhibited the GCl responses induced by Hm and, in some cases, glu. GABA-induced GCl responses were not affected by either toxin even at concentrations as high as 10(-3) M. Both toxins also inhibited synaptic cholinergic GCl responses as well as the GCl component of postsynaptic potentials mediated by noncholinergic presynaptic neurons. Studies of 125I-alpha BuTX binding to Aplysia ganglia homogenates demonstrated the presence of a single saturable, high affinity site with a dissociation constant (KD) of 3.6 X 10(-9) M. The pharmacological profile of agents which inhibit 125I-alpha BuTx binding to Aplysia ganglia was similar to the profile of vertebrate ganglionic and brain preparations; d- tubocurarine, nicotine, and carbamylcholine effectively and competitively inhibit binding, whereas hexamethonium and decamethonium are less effective and noncompetitive. Strychnine and bicuculline, agents known to block responses to a variety of agonists in Aplysia, were effective competitive inhibitors of toxin binding in Aplysia and in rat brain. Strychnine is not as potent in inhibiting toxin binding to electric organ preparations. Chloride channel blockers, such as penicillin and picrotoxin, and noncholinergic agonists, such as Hm and glu, had no effect on toxin binding. The alpha-toxins appear to inhibit noncholinergic GCl responses through a cholinergic receptor associated with the Cl- conductance mechanism for the noncholinergic agonist.
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[Abstract] [Full Text]
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