Azaspiracid-1 inhibits bioelectrical activity of spinal cord neuronal networks

Toxicon : Official Journal of the International Society on Toxinology
Nadezhda V KulaginaThomas J O'Shaughnessy

Abstract

Azaspiracid-1 (AZA-1) is a recently identified phycotoxin that accumulates in molluscs and can cause severe human intoxications. For this study, we utilized murine spinal cord and frontal cortex neuronal networks grown over 64 channel microelectrode arrays (MEAs) to gain insights into the mechanism of action of AZA-1 on neuronal cells. Extracellular recordings of spontaneous action potentials were performed by monitoring mean spike rate as an assay of the efficacy of AZA-1 to alter the bioelectrical activity of neurons in the networks. Via slow onset, AZA-1 decreased the mean spike rate of the spinal cord neurons with an IC(50) of ca. 2.1nM, followed by partial recovery of original activity when toxin was removed. Pre-treatment with the GABA(A) receptor antagonist bicuculline led to an increased response of the neuronal networks to AZA-1 exposure and resulted in an irreversible inhibition of spike rate. AZA-1 did not cause any changes in frontal cortex networks upon drug exposure. In addition, whole-cell patch clamp recordings from spinal cord neurons showed that AZA-1 had no significant effect on the voltage-gated sodium (Na(+)) or calcium (Ca(2+)) currents, suggesting that the toxin affected synaptic transmission in the neuro...Continue Reading

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Citations

Aug 19, 2008·Chemical Research in Toxicology·Natalia VilariñoLuis M Botana
Nov 14, 2008·Journal of the American Chemical Society·David A EvansDavid A Favor
Oct 10, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Carmen ValeLuis M Botana
Jan 6, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Zhengyu CaoThomas F Murray
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Feb 24, 2009·Toxicon : Official Journal of the International Society on Toxinology·Reiko UeokaShigeki Matsunaga
Sep 16, 2014·Angewandte Chemie·Vincent Eschenbrenner-LuxHerbert Waldmann
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Jan 30, 2021·Chemical Research in Toxicology·Andrea Boente-JuncalLuis M Botana
Apr 20, 2010·Neurotoxicology·Andrew F M JohnstoneTimothy J Shafer
Sep 3, 2020·Chemical Research in Toxicology·Andrea Boente-JuncalLuis M Botana

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