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

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Abstract

Lead ions (Pb2+) possess characteristics similar to Ca2+. 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 Pb2+ on their contractility and excitability. Acute exposure to extracellular Pb2+ 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, Pb2+ was cardiotoxic and reduced cardiac contractility, making the heart prone to arrhythmias. This was due, in part, to Pb2+ effects on the Cav1.2 channels; however, other channels, transporters or pathways may also be involved. Acute cardiotoxic effects were observed at Pb2+ concentrations achievable during acute lead poisoning. The results suggest how Cav1.2 gating can be affected by divalent cations, such as Pb2, and also suggest a more thorough evaluation of heart function in individuals affected by lead poisoning.

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Authors and Affiliations

  1. Ion Channels Laboratory, Department of Biophysics, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay

    Gonzalo Ferreira de Mattos, Carlos Costa, Florencia Savio & M. Alonso

  2. Centro Interdisciplinario de Neurociencias de Valparaíso, Valparaíso, Chile

    Gonzalo Ferreira de Mattos

  3. Institute for Molecular Medicine, Huntington Beach, CA, USA

    G. L. Nicolson

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  1. Gonzalo Ferreira de Mattos
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  2. Carlos Costa
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  3. Florencia Savio
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  4. M. Alonso
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  5. G. L. Nicolson
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Correspondence to Gonzalo Ferreira de Mattos.

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Funding

This study was funded by grants PDT 7643, CSIC I + D p944, p146, p91, the CSIC human resources for International cooperation program and SNI ANII to GF, GF is also grateful to PEDECIBA, the Millenium Program (Chile) and the Chilean Conicyt International Cooperation Program. GF acknowledges encouragement and support from Drs. Brum, Ríos, Latorre, González, Escobar, Salkoff, Darszon, Bloom and Gundersen.

Conflict of interest

All the authors signing this manuscript declare that they have no conflict of interest with the procedures and results published in this paper. Gonzalo Ferreira declares that he has no conflict of interest. Carlos Costa declares that he has no conflict of interest. Florencia Savio declares that she has no conflict of interest. Mariana Alonso declares that she has no conflict of interest. Garth Nicolson declares that he has no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed according to bio-ethical procedures accepted by the American Association for Laboratory Animal Sciences (IACUC). The protocol was submitted and approved by the Uruguayan Honorary Committee on Animal Ethics (CHEA), submitted by the corresponding author (071140-001788-09).

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This article is part of a Special Issue on ‘Latin America’ edited by Pietro Ciancaglini and Rosangela Itri

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Ferreira de Mattos, G., Costa, C., Savio, F. et al. Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels. Biophys Rev 9, 807–825 (2017). https://doi.org/10.1007/s12551-017-0303-5

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