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

<div>The effect of THIO on hERG channel kinetics. (a) Voltage-dependent activation curves for the control group and group following exposure to 1 <i>μ</i>M THIO for 24 h. Curves were best fits of the data to a Boltzmann function. (b) Voltage clamp protocol and representative current tracing for steady-state inactivation. (c) Normalized steady-state inactivation curves before and after exposure to 1 <i>μ</i>M THIO. (d) Voltage clamp protocol and representative current tracing for the onset of inactivation. (e) Voltage clamp protocol and representative current tracing for the recovery from inactivation. (f) The effect of 1 <i>μ</i>M THIO on the time constant for the onset of inactivation and recovery from inactivation after incubation for 24 h. <span class="nowrap"><svg height="8.55521pt" id="M44" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 34.1002 8.55521" width="34.1002pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g><g transform="matrix(.013,0,0,-0.013,27.661,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g></svg>.</span></div>

Oxidative Medicine and Cellular Longevity

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Figure 2

Figure 2: Thioridazine Induces Cardiotoxicity via Reactive Oxygen Species-Mediated hERG Channel Deficiency and L-Type Calcium Channel Activation 