Chlordecone Inhibits Three Types of Ion Channels in a Neural Cell Line

Inoue, Kazuhide; Nakazawa, Ken; Obama, Tomoko; Fujimori, Kannosuke; Takanaka, Akira

doi:10.1111/j.1600-0773.1990.tb00861.x

Cited by 4 publications

(4 citation statements)

References 11 publications

(9 reference statements)

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“…The first and second effects were described earlier for other types of insecticides, chlordecone [12] and tetramethrin [15] in experiments on cultured nerve cells. However, there are no published data on insecticide-induced slowing of the gating function of the Ca 2 § current.…”

Section: Resultsmentioning

confidence: 91%

“…Close attention in this respect has been paid to the pyrethroids and organochlorines. Pesticides of these classes are able to lower current amplitude through voltage-dependent calciu m [12,14,15], potassium [12][13][14]16], and chlorine [10] channels and modulate sodium channel gating in a complex fashion by inhibiting activation and deactivation of these channels [1,8,14,17].At the same time, the effect of organophosphorus pesticides (dichlorvos, chlorophos, malathion, etc.) on ion channels remains unclear.…”

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confidence: 99%

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Effect of chlorophos (dipterex, trichlorphon) on high-threshold potassium and calcium channels of the neuronal membrane

Bukanova

Solntseva

1996

Bull Exp Biol Med

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The effect of chlorophos (dipterex, trichlorphon) on high-threshold potassium and calcium currents is studied on isolated snail neurons using the patch-clamp technique. Chlorophos (10-I000 ~mol/liter) is found to reversibly lower the peak amplitude of a high-threshold potassium current by 30% on average and exerts two independent effects on a high-threshold calcium current: reversible lowering of the peak amplitude by 35% on average and, in 30% of cases, reversible inhibition of its activation, inactivation, and deactivation. This effect is abolished by adding diltiazem (a calcium channel antagonist) in a concentration of 100 p.mol/liter to the medium. Key Words: insecticides; chlorophos; potassium channels; calcium channels; snarl neuronsThe mechanisms by which organic pesticides exert their neurotoxic effect are currently being studied by neuropharmacologists. It has been demonstrated that critical targets of organic pesticides in nervous tissue are ion channels of the surface cell membrane [1]. Close attention in this respect has been paid to the pyrethroids and organochlorines. Pesticides of these classes are able to lower current amplitude through voltage-dependent calciu m [12,14,15], potassium [12][13][14]16], and chlorine [10] channels and modulate sodium channel gating in a complex fashion by inhibiting activation and deactivation of these channels [1,8,14,17].At the same time, the effect of organophosphorus pesticides (dichlorvos, chlorophos, malathion, etc.) on ion channels remains unclear. These compounds are effective inhibitors of acetylcholinesterase, which is thought to be the chief mechanism of their neurotoxic action [4,6,7,11,18]. However, some neurotropic effects of organophosphorus compounds cannot be attributed to the above mechanism, for instance, chlorophos-induced depolarization of the presynaptic terminal [7] or lowered rate of impulse transmission [5,7]. These changes may be due to the action of the pesticide on the ionic conductivity of the neuronal membrane.The aim of the present study was to investigate the effect of chlorophos on the voltage-dependent potassium and calcium channels of the common snail. MATERIALS AND METHODSThe experiments were carried out on isolated nonidentified neurons of the snail Helix pomatia using the patch-clamp technique. Two microelectrodes filled with potassium citrate (2 mol/liter) were introduced into the cell to fix the potential and to record the transmembrane currents. The solution used for recording the potassium currents contained (in mmol/ liter): 100 NaCI, 4 KCI, 5 CaCI 2, 4 MgCI 2, and 5 tris-(oxymethyl)-aminomethane, and that for recording the calcium currents 4 KCI, 10 CaCI 2, 4 MgCI 2, 5 tris-(oxymethyl)-aminomethane, and 95 tetraethylammo-

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Section: Resultsmentioning

confidence: 91%

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confidence: 99%

Effect of chlorophos (dipterex, trichlorphon) on high-threshold potassium and calcium channels of the neuronal membrane

Bukanova

Solntseva

1996

Bull Exp Biol Med

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“…The concentration of CLD that killed 50% of DA neurons after a 5-day exposure was estimated at 7.9 µM. Interestingly, concentrations of this order were also reported to reduce Ca 2+ and K + channel currents and cause the dysfunction of the Na/K ATPase in catecholaminergic PC12 cells [57]. Whether these activity defects also contribute to CLD-induced DA cell death in our model system, however, remains to be established.…”

Section: Neurotoxic Effects Of Cld On Midbrain-cultured Da Neuronsmentioning

confidence: 82%

The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms

Parrales-Macias

Michel

Tourville

et al. 2023

Cells

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Chlordecone (CLD) is an organochlorine pesticide (OCP) that is currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase the risk of Parkinson’s disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key characteristics of Parkinsonism-like neurodegeneration. For that, we used culture systems of mouse midbrain dopamine (DA) neurons and glial cells, together with the nematode C. elegans as an in vivo model organism. We established that CLD kills cultured DA neurons in a concentration- and time-dependent manner while exerting no direct proinflammatory effects on glial cells. DA cell loss was not impacted by the degree of maturation of the culture. The use of fluorogenic probes revealed that CLD neurotoxicity was the consequence of oxidative stress-mediated insults and mitochondrial disturbances. In C. elegans worms, CLD exposure caused a progressive loss of DA neurons associated with locomotor deficits secondary to alterations in food perception. L-DOPA, a molecule used for PD treatment, corrected these deficits. Cholinergic and serotoninergic neuronal cells were also affected by CLD in C. elegans, although to a lesser extent than DA neurons. Noticeably, CLD also promoted the phosphorylation of the aggregation-prone protein tau (but not of α-synuclein) both in midbrain cell cultures and in a transgenic C. elegans strain expressing a human form of tau in neurons. In summary, our data suggest that CLD is more likely to promote atypical forms of Parkinsonism characterized by tau pathology than classical synucleinopathy-associated PD.

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“… perturbation of neurotransmitters such as dopamine, epinephrine, norepinephrine, serotonin, beta-endorphin, enkephalin and gamma-aminobutyric acid [ 50 , 83 – 100 ]. leakage of intracellular calcium [ 26 , 101 – 106 ]. …”

Section: Resultsmentioning

confidence: 99%

Public health and chronic low chlordecone exposure in Guadeloupe, Part 1: hazards, exposure-response functions, and exposures

Nedellec¹,

Rabl

Dab

2016

Environ Health

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BackgroundInhabitants of Guadeloupe are chronically exposed to low dose of chlordecone via local food. The corresponding health impacts have not been quantified. Nevertheless the public authority implemented an exposure reduction program in 2003. We develop methods for quantifying the health impacts of chlordecone and present the results in 2 articles: 1. hazard identification, exposure-response functions (ERF) and exposure in Guadeloupe, 2. Health impacts and benefits of exposure reduction. Here is the first article.MethodsRelevant data are extracted from publications searched in Medline and Toxline. Available knowledges on mode of action and key-event hazards of chlordecone are used to identify effects of chlordecone that could occur at low dose. Then a linear ERF is derived for each possible effect. From epidemiological data, ERF is the delta relative risk (RR-1) divided by the corresponding delta exposure. From animal studies, ERF is the benchmark response (10 %) divided by the best benchmark dose modeled with BMDS2.4.0. Our goal is to obtain central values for the ERF slopes, applicable to typical human populations, rather than lower or upper bounds in the most sensitive species or sex.ResultsWe derive ERFs for 3 possible effects at chronic low chlordecone dose: cancers, developmental impairment, and hepatotoxicity. Neurotoxicity in adults is also a possible effect at low dose but we lack quantitative data for the ERF derivation. A renal toxicity ERF is derived for comparison purpose. Two ERFs are based on epidemiological studies: prostate cancer in men aged >44y (0.0019 per μg/Lblood) and altered neurodevelopment in boys (−0.32 QIpoint per μg/Lcord-blood). Two are based on animal studies: liver cancer (2.69 per mg/kg/d), and renal dysfunction in women (0.0022 per mg/kg/d).ConclusionThe methodological framework developed here yields ERFs for central risk estimates for non-genotoxic effects of chemicals; it is robust with regard to models used. This framework can be used generally to derive ERFs suitable for risk assessment and for cost-benefit analysis of public health decisions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0160-x) contains supplementary material, which is available to authorized users.

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Chlordecone Inhibits Three Types of Ion Channels in a Neural Cell Line

Cited by 4 publications

References 11 publications

Effect of chlorophos (dipterex, trichlorphon) on high-threshold potassium and calcium channels of the neuronal membrane

Effect of chlorophos (dipterex, trichlorphon) on high-threshold potassium and calcium channels of the neuronal membrane

The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms

Public health and chronic low chlordecone exposure in Guadeloupe, Part 1: hazards, exposure-response functions, and exposures

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