Developmental exposure to lead causes inherent changes on voltage-gated sodium channels in rat hippocampal CA1 neurons

Yan, Dan; Wang, L.; Ma, Fang-li; Deng, Haitao; Liu, J.; Li, C.; Wang, H.; Chen, J.; Tang, Jue; Ruan, Di‐Yun

doi:10.1016/j.neuroscience.2008.02.016

Cited by 11 publications

(5 citation statements)

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“…TrpM channels can be completely blocked by concentrations of Pb 2+ around 10 μM (Sukumar and Beech 2010). Voltage-gated sodium channels in hippocampal CA1 neurons have also been shown to be inhibited and inactivated by Pb 2+ concentrations around 100 μM, (Gu et al 2005;Yan et al 2008). The effects on sodium channels due to chronic Pb 2+ exposure during development in rats has been studied by Yan et al (2008).…”

Section: Introductionmentioning

confidence: 99%

“…Voltage-gated sodium channels in hippocampal CA1 neurons have also been shown to be inhibited and inactivated by Pb 2+ concentrations around 100 μM, (Gu et al 2005;Yan et al 2008). The effects on sodium channels due to chronic Pb 2+ exposure during development in rats has been studied by Yan et al (2008). Lead ions have also been reported to reversibly inhibit delayed and transient outward potassium currents in hippocampal neurons (Madeja et al 1995(Madeja et al , 1997Yu et al 2003).…”

Section: Introductionmentioning

confidence: 99%

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Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels

et al. 2017

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Lead ions (Pb) possess characteristics similar to Ca. Because of this and its redox capabilities, lead causes different toxic effects. The neurotoxic effects have been well documented; however, the toxic effects on cardiac tissues remain allusive. We utilized isolated guinea pig hearts and measured the effects of Pb on their contractility and excitability. Acute exposure to extracellular Pb had a negative inotropic effect and increased diastolic tension. The speed of contraction and relaxation were affected, though the effects were more dramatic on the speed of contraction. Excitability was also altered. Heart beat frequency increased and later diminished after lead ion exposure. Pro-arrhytmic events, such as early after-depolarization and a reduction of the action potential plateau, were also observed. In isolated cardiomyocytes and tsA 201 cells, extracellular lead blocked currents through Cav1.2 channels, diminished their activation, and enhanced their fast inactivation, negatively affecting their gating currents. Thus, Pb was cardiotoxic and reduced cardiac contractility, making the heart prone to arrhythmias. This was due, in part, to Pb effects on the Cav1.2 channels; however, other channels, transporters or pathways may also be involved. Acute cardiotoxic effects were observed at Pb concentrations achievable during acute lead poisoning. The results suggest how Cav1.2 gating can be affected by divalent cations, such as Pb, and also suggest a more thorough evaluation of heart function in individuals affected by lead poisoning.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels

et al. 2017

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“…Gilbert and Mack 1998; Gilbert et al 1996, 1999a, b; Lasley et al 1993). Among lead’s effects in the hippocampus are changes in muscarinic modulation (Cory-Slechta and Pokora 1995; Tang et al 2008; Wang et al 2007), N-methyl-D-aspartate receptor function (Gilbert and Lasley 2007; Guilarte 1997; White et al 2007), voltage-gated sodium channels (Yan et al 2008), learning-induced activation of calcium-dependent protein kinase C (Vazquez and Pena de Ortiz 2004; Xu et al 2005) and neurogenesis in adults (Gilbert et al 2005; Verina et al 2007). Other delayed effects of developmental lead exposure include a reduced ability to recover from stroke (Schneider and Decamp 2007) and an increase in the likelihood of such degenerative diseases as Alzheimer’s (White et al 2007; Wu et al 2008; Zawia and Basha 2005) and Parkinsonism (Landrigan et al 2005; Winkel et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Variations at a quantitative trait locus (QTL) affect development of behavior in lead-exposed Drosophila melanogaster

Hirsch¹,

Possidente²,

Averill³

et al. 2009

NeuroToxicology

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We developed Drosophila melanogaster as a model to study correlated behavioral, neuronal and genetic effects of the neurotoxin lead, known to affect cognitive and behavioral development in children. We showed that, as in vertebrates, lead affects both synaptic development and complex behaviors (courtship, fecundity, locomotor activity) in Drosophila. By assessing differential behavioral responses to developmental lead exposure among recombinant inbred Drosophila lines (RI), derived from parental lines Oregon R and Russian 2b, we have now identified a genotype by environment interaction (GEI) for a behavioral trait affected by lead. Drosophila Activity Monitors (TriKinetics, Waltham, MA), which measure activity by counting the number of times a single fly in a small glass tube walks through an infrared beam aimed at the middle of the tube, were used to measure activity of flies, reared from eggs to 4 days of adult age on either control or lead-contaminated medium, from each of 75 RI lines. We observed a significant statistical association between the effect of lead on average daytime activity across lines and one marker locus, 30AB, on chromosome 2; we define this as a Quantitative Trait Locus (QTL) associated with behavioral effects of developmental lead exposure. When 30AB was from Russian 2b, lead significantly increased locomotor activity, whereas, when 30AB was from Oregon R, lead decreased it. 30AB contains about 125 genes among which are likely “candidate genes” for the observed lead-dependent behavioral changes. Drosophila are thus a useful, underutilized model for studying behavioral, synaptic and genetic changes following chronic exposure to lead or other neurotoxins during development.

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“…The anomalous excitation of nervous cells associated with the plasticity of sodium channels was one of important reasons of producing neuropathic pain [12,16] . Lead that inhibited the activation and accelerated the inactivation of I Na caused the internal Na + concentration to decrease, which might be the possible reasons for lead inhibiting I Na [5,18] . It was likely that Pb 2+ bound to the transmembrane protein amino acid residue and closed voltage sensor, thus inducing conformational changes.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, trapping of IIS4 would slow the outward movement of the voltage sensor, thus the activation of the sodium channel was delayed. The Pb 2+ binding to an intracellular site elevated the threshold of the activation curve of the sodium current to the negative direction [17][18][19] . Pb 2+ caused a negative shift of steady-state inactivation, suggesting that the binding of Pb 2+ would shift sodium channel to the inactivated state, and prevent its recovery from the inactivated state to the resting state, thus shifting the voltage dependence to a more negative membrane potential.…”

Section: Discussionmentioning

confidence: 99%

Effects of SO2 derivatives on sodium currents in acutely isolated rat hippocampal lead-exposed neurons

2008

SCI CHINA SER C

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In this study, the effects of acute SO2 derivatives and chronic lead exposure together on sodium currents (I(Na)) were investigated in acutely isolated rat hippocampal neurons by using the whole-cell patch clamp techniques. We found that chronic lead exposure hardly reduced the amplitudes of I(Na). In the normal condition, sodium current started to appear at around -70 mV, and reached the peak current at around -40 mV. After chronic lead exposure, the data changed to -70 and -30 mV. After adding SO2 derivatives, the data changed to -80 and -40 mV, respectively. SO2 derivatives caused a significant increase of I(Na) in hippocampal chronic-lead exposed neurons. Chronic lead exposure induced a right shift of the activation curve and a left shift of the inactivation curve of sodium channels. SO2 derivatives caused negative shifts of the activation and inactivation curves of I(Na) in hippocampal chronic-lead exposed neurons. Lead exposure put off the time reaching the peak of I(Na) activation. SO2 derivatives increased the time constants of inactivation after lead exposure. The interaction of lead and SO2 derivatives with voltage-dependent sodium channels may lead to changes in electrical activity and contribute to worsening the neurotoxicological damage.

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Developmental exposure to lead causes inherent changes on voltage-gated sodium channels in rat hippocampal CA1 neurons

Cited by 11 publications

References 50 publications

Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels

Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels

Variations at a quantitative trait locus (QTL) affect development of behavior in lead-exposed Drosophila melanogaster

Effects of SO2 derivatives on sodium currents in acutely isolated rat hippocampal lead-exposed neurons

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