Oxaliplatin, a new widely used anticancer drug, displays frequent, sometimes severe, acute sensory neurotoxicity accompanied by neuromuscular signs that look like the symptoms observed in tetany and myotonia. The whole cell patch-clamp technique was employed to investigate the oxaliplatin effects on the electrophysiological properties of short-term cultured dorsal unpaired median (DUM) neurons isolated from the CNS of the cockroach Periplaneta americana. Within the clinical concentration range, oxaliplatin (40–500 μM), applied intracellularly, decreased the amplitude of the voltage-gated sodium current resulting in a reduction of half the amplitude of the action potential. For comparison, two other platinum derivatives, cisplatin and carboplatin, were found to be ineffective at reducing the sodium current amplitude. In addition, we compared the oxaliplatin action to those of its metabolites dichloro-diaminocyclohexane platinum (dach-Cl₂-platin) and oxalate. Oxalate (500 μM) was found to be effective, like oxaliplatin, at reducing the inward sodium current amplitude, whereas dach-Cl₂-platin (500 μM) failed to change the current amplitude. Interestingly, the effect of oxalate or oxaliplatin could be mimicked by using intracellularly applied 10 mM bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA), known as chelator of calcium ions. We concluded that oxaliplatin was capable of altering the voltage-gated sodium channels through a pathway involving calcium ions probably immobilized by its metabolite oxalate. The medical interest of preventing acute neurotoxic side effects of oxaliplatin by infusing Ca²⁺and Mg²⁺is discussed.

N,N-Diethyl-3-methylbenzamide (deet) remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system.

Primary root growth in the absence or presence of exogenous NO₃^– was studied by a quantitative genetic approach in a recombinant inbred line (RIL) population of Medicago truncatula. A quantitative trait locus (QTL) on chromosome 5 appeared to be particularly relevant because it was seen in both N-free medium (LOD score 5.7; R²=13.7) and medium supplied with NO₃^– (LOD score, 9.5; R²=21.1) which indicates that it would be independent of the general nutritional status. Due to its localization exactly at the peak of this QTL, the putative NRT1-NO₃^– transporter (Medtr5g093170.1), closely related to Arabidopsis AtNRT1.3, a putative low-affinity nitrate transporter, appeared to be a significant candidate involved in the control of primary root growth and NO₃^– sensing. Functional characterization in Xenopus oocytes using both electrophysiological and ¹⁵NO₃^– uptake approaches showed that Medtr5g093170.1, named MtNRT1.3, encodes a dual-affinity NO₃^– transporter similar to the AtNRT1.1 ‘transceptor’ in Arabidopsis. MtNRT1.3 expression is developmentally regulated in roots, with increasing expression after completion of germination in N-free medium. In contrast to members of the NRT1 superfamily characterized so far, MtNRT1.3 is environmentally up-regulated by the absence of NO₃^– and down-regulated by the addition of the ion to the roots. Split-root experiments showed that the increased expression stimulated by the absence of NO₃^– was not the result of a systemic signalling of plant N status. The results suggest that MtNRT1.3 is involved in the response to N limitation, which increases the ability of the plant to acquire NO₃^– under N-limiting conditions.

Although molecular biology provides new insights into the subunit compositions and the stoichiometries of insect neuronal nicotinic acetylcholine receptors (nAChRs), our knowledge about the phosphorylation/dephosphorylation mechanisms of native neuronal nAChRs is limited. The regulation of α-bungarotoxin-resistant nAChRs was studied on dissociated adult dorsal unpaired median neurons isolated from the terminal abdominal ganglion of the cockroachPeriplaneta americana, using whole-cell, patch-clamp technique. Under 0.5 μM α-bungarotoxin treatment, pressure ejection application of nicotine or acetylcholine onto the cell body induced an inward current exhibiting a biphasic current-voltage relationship. We found that two distinct components underlying the biphasic curve differed in their ionic permeability and pharmacology (one being sensitive to d-tubocurarine, and the other affected only by mecamylamine and α-conotoxin ImI). This indicated that two types of α-bungarotoxin-resistant nAChRs (named nAChR1 and nAChR2) mediated the nicotinic response. These two components were also differentially sensitive to rundown and intracellular messengers. Intracellular application of 0.1 mM cAMP only increased the current amplitude mediated by nAChR1. Using forskolin (1 μM), W7 and H89, we demonstrated that adenylyl cyclase, sensitive to calcium/calmodulin complex, regulated nAChR1 via a cAMP/cAMP-dependent protein kinase cascade. By contrast, internal cAMP concentration higher than 0.1 mM reduced the current amplitude. This effect, mimicked by high external concentration of forskolin (100 μM) and IBMX, was reversed by okadaic acid, suggesting the implication of a protein phosphatase. Using KN-62, we demonstrated that calmodulin-Kinase II also modulated directly and indirectly nAChR1, via an inhibition of the phosphatase activity. Finally, we reported that phosphorylation/dephosphorylation of nAChR1 strongly affected the action of the widely used neonicotinoid insecticide imidacloprid.