Photosensitization Reaction-Induced Electrophysiological Response of Myocardial Cells Dependent on Subcellular Photosensitizer Distribution

摘要

We have demonstrated photosensitization reaction-induced electrical conduction block of myocardial tissue. Subcellular distribution of photosensitizer and electrophysiological cell response to this photosensitization reaction were studied with rat myocardial cells, in order to clarify the mechanism of the myocardial electrical conduction block with photodynamic therapy (PDT). Photofrin® was used as photosensitizer in this study. The subcellular distribution of the photosensitizer was obtained by microscopic fluorescent observation. The sites of photosensitizer localization were determined by organelle fluorescent probe, Rhodamine® 123, to specify the mitochondria location. The myocardial cell response to the photosensitization reaction was studied by the observation of intracellular Ca~(2+) dynamics. Intracellular free Ca~(2+) concentration in the myocardial cells was measured with fluorescent Ca~(2+) indicator, Fluo-4 AM, by a high-speed Nipkow-type confocal laser microscope during the PDT when the photosensitizer was distributed outside the cells or localized to intracellular compartments. We concluded that the Ca~(2+) influx accompanied by cell membrane damage when the photosensitizer was distributed outside the cells or on the cell membrane was the possible mechanism of the myocardial electrical conduction block with the photosensitization reaction.