Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels
- PDF / 8,924,414 Bytes
- 19 Pages / 595.276 x 790.866 pts Page_size
- 7 Downloads / 151 Views
REVIEW
Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels Gonzalo Ferreira de Mattos 1,2 & Carlos Costa 1 & Florencia Savio 1 & M. Alonso 1 & G. L. Nicolson 3
Received: 18 May 2017 / Accepted: 28 July 2017 # International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany 2017
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 Pb 2 +
This article is part of a Special Issue on ‘Latin America’ edited by Pietro Ciancaglini and Rosangela Itri * Gonzalo Ferreira de Mattos [email protected]
1
Ion Channels Laboratory, Department of Biophysics, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
2
Centro Interdisciplinario de Neurociencias de Valparaíso, Valparaíso, Chile
3
Institute for Molecular Medicine, Huntington Beach, CA, USA
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. Keywords Lead poisoning . Lead exposure . Isolated heart . L-type Ca2+ channels . Cav1.2 channels . Gating currents inactivation
Introduction Lead is a post-transition heavy metal whose usual ionic form is +2 (Pb2+) (Casas and Sordo 2011). It is basically a nonbiodegradable, toxic material that is found naturally and has widespread human uses, but can also cause significant environmental contamination. Human exposure to organic or inorganic lead can result in acute or chronic poisoning. Thus, it is a relevant worldwide health problem (Gidlow 2015). Though lead intoxication in humans has diminished since the prohibition of lead addition to gasoline and paint, it is still a
Data Loading...
