The calcium-calmodulin-dependent protein kinase kinase inhibitor, STO-609, inhibits nicotine-induced currents and intracellular calcium increase in insect neurosecretory cells.

Autor: Taha M; Laboratoire Physiologie, Ecologie et Environnement (P2E), USC-INRAE 1328, Université d'Orléans, Orléans, France., Houchat JN; Laboratoire Physiologie, Ecologie et Environnement (P2E), USC-INRAE 1328, Université d'Orléans, Orléans, France., Taillebois E; Laboratoire Physiologie, Ecologie et Environnement (P2E), USC-INRAE 1328, Université d'Orléans, Orléans, France., Thany SH; Laboratoire Physiologie, Ecologie et Environnement (P2E), USC-INRAE 1328, Université d'Orléans, Orléans, France.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Jul; Vol. 168 (7), pp. 1281-1296. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1111/jnc.16077
Abstrakt: Insect neuronal nicotinic acetylcholine receptors (nAChRs) are transmembrane receptors that play a key role in the development and synaptic plasticity of both vertebrates and invertebrates and are considered to be major targets of neonicotinoid insecticides. We used dorsal unpaired median (DUM) neurons, which are insect neurosecretory cells, in order to explore the intracellular mechanisms leading to the regulation of insect neuronal nAChRs in more detail. Using whole-cell patch-clamp and fura-2AM calcium imaging techniques, we found that a novel CaMKK/AMPK pathway could be involved in the intracellular regulation of DUM neuron nAChRs. The CaMKK selective inhibitor, STO, reduced nicotinic current amplitudes, and strongly when co-applied with α-Bgt. Interestingly, intracellular application of the AMPK activator, A-76, prevented the reduction in nicotine-induced currents observed in the presence of the AMPK inhibitor, dorsomorphin. STO prevented the increase in intracellular calcium induced by nicotine, which was not dependent on α-Bgt. Currents induced by 1 mM LMA, a selective activator of nAChR2, were reduced under bath application of STO, and mecamylamine, which blocked nAChR2 subtype, inhibited the increase in intracellular calcium induced by LMA. These findings provide insight into potential complex mechanisms linked to the modulation of the DUM neuron nAChRs and CaMKK pathway.
(© 2024 International Society for Neurochemistry.)
Databáze: MEDLINE
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