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University of South Carolina, Columbia, SC
NIEHS Grant Number: 1R21ES013391-01
Ambient particulate matter (PM) exposure has been a public health concern and is responsible for increased cardiopulmonary mortality and morbidity, especially in susceptible populations with compromised cardiovascular function. Epidemiological and clinical studies demonstrate that acute exposure to PM triggers cardiac incidences (such as arrhythmia, angina pectoris, and myocardial infarction) and alters heart rate variability. However, the lack of study at the cellular and ion channel protein levels has impeded the investigators’ development of a mechanistic understanding of PM-produced cardiovascular toxicity. Ion current flow across the cell membrane underlies all the cardiac electrical activity and the alteration of ion channel function accounts for a large variety of cardiac abnormalities. The investigators’ preliminary studies show that surrogate PM ROFA (residual oil fly ash) extract causes changes in the electrical activity of the whole-heart and the action potential waveforms of single myocytes. Previous findings by others demonstrated that inorganic metals such as V and Ni affect Ca 2+ and K + currents in the excitable tissues. The metallic elements are common constituents of atmospheric PM. Thus, the investigators hypothesize that acute exposure to the bioactive constituents of PM affects cardiac ion channel function by directly acting on ion channel proteins and by altering the signaling pathways involved in ion channel regulation. Three specific aims are designed to evaluate the changes of cardiac ion channels by the leachable components of ambient PM and ROFA samples using electrophysiological techniques in rat cardiac preparations: (1) to study the PM-induced abnormal cardiac electrical activity in isolated perfused hearts; (2) to study the PM-caused change of electrical excitability in single cardiac myocytes; and (3) to identify the ion channel proteins responsible for PM-induced changes of cardiac electrical activity. The long-term goal is to define the signaling pathways that are disrupted by PM exposure and to establish a profile of the vulnerable cardiac ion channels that respond to exposure to various PM constituents. The findings of this study will advance our understanding of PM-induced cardiotoxicity at the cellular and molecular levels and provide policy-makers and the public with new evidence for the necessity of controlling the level of ambient PM pollution.