부산대학교 도서관

Smoking is well known as a major risk factor of cardiovascular diseases. However, the direct effects of smoking substances on cardiomyocyte and its cellular mechanism have not been fully clarified. In this study, we examined the effects of CSE on the contractile function, intracellular Ca2+ dynamics, and mitochondrial function using cultured or freshly isolated rat ventricular myocytes and human iPS-derived cardiomyocytes. CSE at concentration above 0.1% decreased the spontaneous beating rate of cultured rat cardiomyocytes in a time- and concentration-dependent manner. 1% CSE reduced the cell shortening of freshly isolated cardiomyocytes. Similar contractile dysfunctions were also observed in human iPS-derived cardiomyocytes. In contrast, 1% CSE increased intracellular Ca2+ transient amplitude, often triggered spike-shaped Ca2+ transients. Kinetic analysis indicated that CSE enhanced Ca2+ uptake into the SR. These results suggest that abnormal Ca2+ entry/release in the SR occurred upon CSE treatment. Furthermore, CSE induced a decrease in mitochondrial membrane potential, an early event in cellular damage that can be caused by abnormal intracellular Ca2+ dynamics. Taken together, these results demonstrate that CSE weakens contractile function of cardiomyocytes via abnormal Ca2+-medicated dysregulation of mitochondrial function.