Inhibitory effect of Cd2+ on glycine-induced chloride current in rat hippocampal neurons

Wang, Shu; Gu, Yan; Wang, Huili; Li, Xinmei; Wang, Ming; Sun, Liwei; Ruan, Di‐Yun

doi:10.1016/j.brainresbull.2006.03.019

Cited by 9 publications

(1 citation statement)

References 40 publications

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“…We found cadmium in the MBS at a concentration of about 7 nM. It is unlikely that cadium is the responsible agent in our studies since cadmium inhibits rather than enhances GlyR-mediated currents in dissociated rat hippocampal neurons and has low potency, with an IC50 of 1.27 mM (Wang et al, 2006). It was also found to act at a site distinct from that mediating zinc actions.…”

Section: Discussionmentioning

confidence: 77%

Contaminating levels of zinc found in commonly-used labware and buffers affect glycine receptor currents

Cornelison

Mihic

2014

Brain Research Bulletin

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Zinc is an allosteric modulator of glycine receptor function, enhancing the effects of glycine at nM to low μM concentrations, and inhibiting its effects at higher concentrations. Because of zinc’s high potency at the glycine receptor, there exists a possibility that effects attributed solely to exogenously-applied glycine in fact contain an undetected contribution of zinc acting as an allosteric modulator. We found that glycine solutions made up in standard buffers and using deionized distilled water produced effects that could be decreased by the zinc chelator tricine. This phenomenon was observed in three different vials tested and persisted even if vials were extensively washed, suggesting the zinc was probably present in the buffer constituents. In addition, polystyrene, but not glass, pipets bore a contaminant that enhanced glycine receptor function and that could also be antagonized by tricine. Our findings suggest that without checking for this effect using a chelator such as tricine, one cannot assume that responses elicited by glycine applied alone are not necessarily also partially due to some level of allosteric modulation by zinc.

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Section: Discussionmentioning

confidence: 77%

Contaminating levels of zinc found in commonly-used labware and buffers affect glycine receptor currents

Cornelison

Mihic

2014

Brain Research Bulletin

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Effects of Cd2+ on transient outward and delayed rectifier potassium currents in acutely isolated rat hippocampal CA1 neurons

Shu

Xing

Tang

et al. 2008

Naunyn-Schmied Arch Pharmacol

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The effects of cadmium (Cd(2+)) on the transient outward potassium current (I(A)) and delayed rectifier potassium current (I(K)) were investigated in acutely dissociated rat hippocampal CA1 neurons using the whole-cell patch-clamp technique. The results showed that Cd(2+) inhibited the amplitudes of I(A) and I (K) in a reversible and concentration-dependent manner, with half-maximal inhibitive concentration (IC(50)) values of 546+/-59 and 749+/-53 microM, and the inhibitory effect of Cd(2+) was voltage dependent. Cd(2+) significantly shifted the steady-state activation and inactivation curve of I(A) to more positive potentials. In contrast, Cd(2+) caused a relatively less but still significant positive shift in the activation of I(K) without effect on the inactivation curve. Cd(2+) significantly slowed the recovery from inactivation of I(K) but had no effect on the recovery time course of I(A). The results suggest that the modulation of I(A) and I(K) was most likely mediated by the interaction of Cd(2+) with a specific site on the potassium-channel protein rather than by screening of bulk surface-negative charge. The effects of Cd(2+) on the voltage-gated potassium currents may be a possible contributing mechanism for the Cd(2+)-induced neurotoxic damage. In addition, the effects of Cd(2+) on the potassium currents at concentrations that overlap with its effects on calcium currents raise concerns about its use in pharmacological or physiological studies.

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Transcriptional responses indicate attenuated oxidative stress in the springtail Folsomia candida exposed to mixtures of cadmium and phenanthrene

et al. 2013

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Since the 'omics revolution', the assessment of toxic chemical mixtures has incorporated approaches where phenotypic endpoints are connected to a mechanistic understanding of toxicity. In this study we determined the effect of binary mixtures of cadmium and phenanthrene on the reproduction of Folsomia candida and investigated the cellular mechanisms underlying this response. Mixture toxicity modeling showed an antagonistic deviation from concentration addition for reproduction effects of the mixtures. Subsequent transcriptional response analysis was done using five mixtures at the modeled 50 % effect level for reproduction. The transcription profiles of 86 high throughput RT-qPCR assays were studied by means of partial least squares regression analysis. The first and second principal components (PCs) were correlated with global responses to cadmium and phenanthrene, while correlations with the mixture treatments were found in the higher PCs. Specifically associated with the mixture treatments were a biotransformation phase II gene, four mitochondrial related genes and a gene involved in the biosynthesis of antioxidant selenoproteins. Membrane integrity related gene inductions were correlated with the single phenanthrene treatment but not with the mixtures. Immune and inflammatory response assays did not correlate with any of the mixtures. These results suggest moderated oxidative stress, a higher mitochondrial maintenance and less compromised membrane function in the mixture exposed samples compared to the separate cadmium or phenanthrene exposures. The antagonism found for inhibition of reproduction may partially originate from these differences. Mechanistic studies on mixture toxicity can ultimately aid risk assessment by defining relevant toxicity pathways in organisms exposed to real-world mixture exposures present in the field.

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Inhibitory effect of Cd2+ on glycine-induced chloride current in rat hippocampal neurons

Cited by 9 publications

References 40 publications

Contaminating levels of zinc found in commonly-used labware and buffers affect glycine receptor currents

Contaminating levels of zinc found in commonly-used labware and buffers affect glycine receptor currents

Effects of Cd2+ on transient outward and delayed rectifier potassium currents in acutely isolated rat hippocampal CA1 neurons

Transcriptional responses indicate attenuated oxidative stress in the springtail Folsomia candida exposed to mixtures of cadmium and phenanthrene

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