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ZINC PRODUCES A TRANSMURAL VOLTAGE GRADIENT AND DISRUPTION OF INTERCELLULAR COMMUNICATION IN THE HEART
Citation:
Graff, D., W. Cascio, B. MullerBorer, A. Aghajanian, P. Sama, G. Yan, AND R B. Devlin. ZINC PRODUCES A TRANSMURAL VOLTAGE GRADIENT AND DISRUPTION OF INTERCELLULAR COMMUNICATION IN THE HEART. Presented at American Thoracic Society Annual Conference, San Diego, CA, March 20 - 25, 2005.
Description:
Ambient air pollution particulate matter (PM) exposure contributes to serious arrhythmia in high-risk individuals. We previously showed that non-cytotoxic doses of zinc sulfate (Zn, 50uM), a metal common to PM from many sources, alters the gene expression of several cardiac ion channels (K+ and Ca2+) and decreases cardiac myocyte beat rate, indicating that Zn may induce an electrical remodeling process, thereby accounting for PM-induced changes in ST-T wave morphology and rhythm disturbances. The cardiac toxicity of Zn was subsequently investigated in rabbit left ventricular wedge preparations (n=2) by assessing the effect of Zn on epicardial and endocardial action potential (AP) characteristics, mechanical properties, and the ECG. A 50uM Zn perfusion decreased contraction by 89% and preferentially shortened the epicardial AP 36% at APD50 and 23% at APD90, caused ST elevation to 30% of R wave amplitude and increased the QRS duration by 7%. Because cellular coupling is vital for propagation of electrical impulses and electrotonic interaction, we assessed the effects of 50uM Zn on gap junction communication (GJC) between cultured rat cardiac myocytes using the fluorescence recovery after photobleaching (FRAP) technique. A 2-hour Zn exposure (n=20) decreased recovery rate 26% while a 4-hour (n=21) exposure decreased recovery rate by 47%, indicating significant disruption in GJC. In conclusion, Zn exposure induces a broad range of physiological effects in the heart that may account for ST-T wave changes and PM-associated risk of arrhythmia. These data suggest that cardiac mortality associated with PM may be mediated in part by Zn and provides biological plausibility to previous epidemiologic and toxicologic studies. (This abstract does not reflect US EPA policy.)