Thioridazine Induces Cardiotoxicity via Reactive Oxygen Species-Mediated hERG Channel Deficiency and L-Type Calcium Channel Activation

Figure 7

Effects of THIO (1 μM, 24 h) on currents of voltage-gated L-type Ca²⁺ channels. (a) ROS accumulation as measured by DCFDA oxidation in Figure 5(a). Values are from three independent experiments and normalized to control. THIO induced a significant increase in intracellular ROS, which was significantly decreased in NRVMs pretreated with NAC for 1 h. Original magnification, ×200. (b) NRVMs were treated as in Figure 5(a) and the mean fluorescence intensity was quantified by flow cytometry. (c) Representative Western blots of ox-CaMKII (top), pan-CaMKII (middle), and actin (bottom). Oxidized and total protein levels are presented relative to actin. Data are presented as the for each group (). (d) Voltage protocol and representative current. (e) - relationships of current (-9). (f) Representative confocal images of [Ca²⁺]_i changes before and after 30 mM KCl exposure for control (left column) and 1 μM THIO (right column). (g) Mean values of the FI/F0 ratio during the 300 s scanning in the presence of 30 mM KCl. (h) The average ratio of in each group after 30 mM KCl stimulation. . Drug treatment occurred 24 h prior to analysis. vs. control and vs. THIO.

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