Effects of lead on voltage-gated sodium channels in rat hippocampal CA1 neurons

Gu, Yan; Wang, L.; Xia, Cheng; Guo, Fei; Ruan, Di‐Yun

doi:10.1016/j.neuroscience.2005.02.039

Cited by 21 publications

(12 citation statements)

References 34 publications

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“…Lead can interfere with cellular physiology (Patrick, 2006b) and it can increase antioxidant enzymes and lipid peroxidation products in both developing (Kiran Kumar et al, 2008) and adult rat brain (Bennet et al, 2007). Although lead permeates all the tissues, some components of brain, for example hippocampus, exhibit greater damage on lead exposure (EPA, 1999), leading to hippocampal dysfunction (Munoz et al, 1988) and blockage of ion channels in hippocampus (Gu et al, 2005). This might have resulted in the disturbances in memory and longterm potentiation (Altman et al, 1993;Adonaylo and Oteiza, 1999;Bennet et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Influence of lead acetate on glutathione and its related enzymes in different regions of rat brain

Bokara

Blaylock

Denise

et al. 2009

J of Applied Toxicology

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This study is intended to determine the effect of lead acetate on glutathione and its associated enzymes of rat brain. Wistar male rats were treated with lead acetate (500 ppm) through drinking water for a period of 8 weeks and parallel controls were maintained. They were sacrificed at the first, fourth and eighth week to isolate whole brains, which were separated into cerebellum, hippocampus, frontal cortex and brain stem. The data indicate enhanced (P < 0.05) glutathione peroxidase (G-Px) activity at most of the intervals for cerebellum, frontal cortex and brain stem, suggesting conversion of GSH to GSSG, while the hippocampus showed decreased levels. In contrast, glutathione reductase (GR) decreased significantly (P < 0.05) in cerebellum, frontal cortex and brain stem at all intervals except the fourth week in frontal cortex and brain stem. Hippocampus exhibited a gradual and significant (P < 0.05) increase in GR activity. Glutathione-S-transferase (GSTase) activity increased with exposure time in all four brain tissues, showing protection against lead acetate toxicity. The GSH and GSSG levels correlated well with the activities of GPx, GR and GSTase in all four regions of the brain. Overall the results indicate that lead acetate affects glutathione-related enzymes differentially and these changes can be attributed to differences in tissue susceptibility.

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Section: Introductionmentioning

confidence: 99%

Influence of lead acetate on glutathione and its related enzymes in different regions of rat brain

Bokara

Blaylock

Denise

et al. 2009

J of Applied Toxicology

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“…It is well known that metals interact with ion channels on the plasma membrane, competing with essential ions for binding sites and modifying the permeability of the cell (Arhem 1980; Kiss & Osipenko 1994a,b; Franchet et al. 1997; Gu et al. 2005).…”

Section: Discussionmentioning

confidence: 99%

“…2005). Although little is known about the mechanism of action and the molecular target of these elements, in the case of lead it has been postulated that it acts on the external voltage sensor of sodium channels (Gu et al. 2005).…”

Section: Discussionmentioning

confidence: 99%

The impact of metals on the reproductive mechanisms of the ascidian Ciona intestinalis

et al. 2011

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Environmental pollution due to anthropogenic activities may exert an adverse impact on the reproductive mechanisms of animals. In particular, environmental chemicals introduced into seawater are able to disrupt the normal development and function of the reproductive system of marine animals. In this study, we have used the whole‐cell voltage clamp technique to examine the effects of four metals – lead, cadmium, mercury, and zinc – on reproductive mechanisms of the marine ascidian Ciona intestinalis (tunicates). In particular, we measured the effect of metals on plasma membrane electrical properties, the steady‐state conductance, the fertilization current in the mature oocyte, and larval development. Results show that oocyte voltage‐gated sodium currents are significantly reduced by all four metals, steady‐state conductance is affected only by zinc, and post‐fertilization contraction is inhibited only by lead. The fertilization current is suppressed in the presence of zinc and mercury. Embryo development up to larval stage is inhibited by zinc and mercury exposure with a reversible effect; however, a long‐term effect on larval morphology was observed. After exposure to cadmium, fertilization occurs but gives rise to abnormal larval development. These findings highlight the point that exposure to metals represents a significant risk factor for the physiology of reproduction of marine species and suggest a possible role of the C. intestinalis as a bioindicator for marine pollution monitoring.

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“…These results prompted us to focus directly on lead's effect on action potential (AP), which is the result of the concerted action of a rich variety of selectively permeant voltage‐dependent ionic channels. Previous studies showed that lead had inhibitory effects on inward sodium and transient outward potassium currents of neurons at micromolar concentrations but had no significant effects on delayed rectifier potassium currents (Dai et al, 2001; Gu et al, 2005). Some studies that specifically examined effects of lead on voltage‐dependent calcium channels (VDCCs) demonstrated potent blocking ability of lead on some of the identified subtypes of VDCCs at submicromolar levels (Büsselberg et al, 1991, 1994; Bernal et al, 1997; Peng et al, 2002; Atchison, 2003).…”

mentioning

confidence: 98%

Excitatory effects of low‐level lead exposure on action potential firing of pyramidal neurons in CA1 region of rat hippocampal slices

Yan

Xia

Ma³

et al. 2008

J of Neuroscience Research

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Lead is putatively regarded as an environmental neurotoxicant. Long-term low-level lead exposure causes cognitive deficits, but the mechanism remains to be elucidated. In the present study, the excitatory effects of low-level lead exposure on action potential (AP) firing of pyramidal neurons in CA1 region of rat hippocampal slices and the pathway through which lead induced these effects were studied with conventional whole-cell recording. Low-level lead (0.5 and 5 microM) exposure did not significantly change either voltage threshold or amplitude, duration, rise time, or rising velocity of single AP; conversely, 5 microM lead exposure significantly increased AP firing rates and reduced spike frequency adaptation. These excitatory effects of 5 microM lead were blocked by mibefradil, a selective blocker of T-type voltage-dependent calcium channels (VDCC), but not by verapamil and omega-conotoxin, selective blockers of L-type and N-type VDCC, respectively. Five micromolar lead could not change the excitability of pyramidal neurons when slices were perfused with calcium-free ACSF. In addition, the effects were abolished by inhibitors of two intracellular calcium release channels: 2-APB, an inhibitor of inositol trisphosphate receptors, and dantrolene, an inhibitor of ryanodine receptors, but not by thapsigargin, an inhibitor of endoplasmic reticulum calcium uptake. These results provide evidence for excitatory neurotoxicity of low-level lead exposure, contribution of T-type VDCC in the entrance of lead into neurons, and a possible involvement of calcium flux alteration during APs in this excitatory neurotoxicity.

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Effects of lead on voltage-gated sodium channels in rat hippocampal CA1 neurons

Cited by 21 publications

References 34 publications

Influence of lead acetate on glutathione and its related enzymes in different regions of rat brain

Influence of lead acetate on glutathione and its related enzymes in different regions of rat brain

The impact of metals on the reproductive mechanisms of the ascidian Ciona intestinalis

Excitatory effects of low‐level lead exposure on action potential firing of pyramidal neurons in CA1 region of rat hippocampal slices

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