Lead and Carbon Monoxide Effects on Human Atrial Action Potential. In Silico Study

Abstract

Exposure to air pollutants like lead (Pb ++ ) and carbon monoxide (CO) IntroductionAir pollution is defined as the presence in the atmosphere of one or more substances in sufficient quantity to produce health alterations. Air pollution causes 4.3 million premature deaths annually [1]. In 2010, the economic cost of health impacts of air pollution in developing countries was around USD 1.7 billion [1].Lead (Pb ++ ) is a toxic agent that can exert adverse health effects in humans. According to the United States Environment Protection Agency (EPA), the Pb ++ is one of the most dangerous air pollutants, affecting multiple human body systems [2]. In general, more than 143.000 people die every year due to illnesses related to Pb ++ [3].Carbon monoxide (CO) is a toxic gas, from incomplete combustion. When people breath, the CO binds to hemoglobin and is significantly retained within the blood reducing the amount of oxygen that it can transport [4].Exposure to these air pollutants contributes to cardiovascular diseases [5]. Epidemiological studies have reported effects such as heart failure, generation of cardiac arrhythmias and decreased heart rate variability [3,[5][6][7][8][9][10][11]. Experimental studies have shown that the Pb ++ blocks the L-type calcium channels [12]. A decrease in Ltype calcium current (I CaL ) is an important mechanism that favors the generation of atrial arrhythmias [13]. Recently, it has been shown that chronic exposure to CO promotes a pathological phenotype of cardiomyocytes, where remodeling leads to an important reduction of the action potential duration (APD) in atrial myocardium increasing the risk of arrhythmias [9,10] and ischemia [14]. This study aims to assess the effects of the Pb ++ and CO at different concentrations on human atrial action potential, using computational simulation. Methods Human atrial cell modelThe Courtemanche-Ramirez-Nattel-Kneller [15,16] membrane formalism was implemented to simulate the electrical activity of human atrial cell. A 0.005 µM of acetylcholine concentration was simulated. The transmembrane voltage (V m ) is given by:where C m is the membrane capacitance (100 pF), I ion is the total membrane current, and I st is the external stimulus current. The model is considered under normal electrophysiological conditions. Model of Pb ++ and CO effects on I CaLWe developed concentration dependent equations to