Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

Background/Purpose

The electropharmacological effect of arsenic trioxide (As₂O₃) is unknown. The present study investigated the effects of As₂O₃ on spontaneous neuronal impulse activity.

Methods

Intracellular recordings and the two-electrode voltage clamp method were used to study the effect of As₂O₃ on the RP4 neuron, the number 4 neuron in the right partial ganglion of the giant African snail (Achatina fulica Ferussac).

Results

The RP4 neuron generated spontaneous action potentials, which were affected by As₂O₃ in a concentration-dependent manner. Extracellular application of 1 or 3 mM As₂O₃ decreased the frequency of spontaneously generated action potentials. At 10 mM, As₂O₃ first depolarized and then elicited irreversible bursts of potential (BoPs) at 60 minutes after administration. At 30 mM, As₂O₃ depolarized the resting membrane potential and abolished the spontaneous action potentials. The BoPs elicited by 10 mM As₂O₃ were blocked when neurons were pretreated with phospholipase C (PLC) inhibitors (10 mM U73122 or 3 mM neomycin). The BoPs elicited by As₂O₃ remained unchanged in the presence of KT5720, verapamil, or calcium replacement solution. Voltage-clamp studies revealed that 10 mM As₂O₃ decreased the fast inward current and had no effect on the steady-state outward current of the neuron.

Conclusion

As₂O₃ at 10 mM elicits BoPs in central snail neurons and this effect may relate to the PLC activity of the neuron, rather than protein kinase A activity, or calcium influxes of the neuron. As₂O₃ at higher concentration irreversibly abolishes the spontaneous action potentials of the neuron.

Key Words:  arsenic trioxide , neurons , phospholipase C , second messenger systems , snails

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