3L-Phosphinothricin modulation of inwardly rectifying K+ channels increased excitability in striatal medium-sized spiny neurons

Abstract : Phosphinotricin (L-PPT) is the active compound of a broad-spectrum herbicide. Acute poisoning with L-PPT has various clinical manifestations, including seizures and convulsions. However, the exact mechanism of L-PPT toxicity remains unclear. The present study addressed the role of L-PPT, in the excitability of striatal medium-sized spiny neurons (MSNs). In whole-cell current-clamp experiments, L-PPT increased the input resistance (Ri), decreased the rheobase and increased the firing frequency of action potentials. In voltage-clamp experiments, L-PPT inhibited the inward-rectifying potassium (Kir) currents. Finally, the effects of L-PPT mimicked the inhibition of Kir channels with Ba2+ on neuronal excitability. Altogether, these results suggest that the herbicide L-PPT is a modulator of Kir channels in MSNs. Thereby, Kir channels are potent regulators of the excitability of MSNs and reduced open probability of these channels would generate a powerful upregulation of neuronal output. This effect may represent a possible mechanism for L-PPT dependent neuronal toxicity.
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https://hal.archives-ouvertes.fr/hal-01406951
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Submitted on : Thursday, December 1, 2016 - 4:57:22 PM
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Laetitia Domingos, Agnès Desrus, Sandra Même, William Même. 3L-Phosphinothricin modulation of inwardly rectifying K+ channels increased excitability in striatal medium-sized spiny neurons. Archives of Toxicology, Springer Verlag, 2016, 90 (7), pp.1719 - 1727. ⟨10.1007/s00204-016-1721-z⟩. ⟨hal-01406951⟩

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