Role of CaMKII and PKA in Early Afterdepolarization of Human Ventricular Myocardium Cell: A Computational Model Study

<div>1 <i>μ</i>M ISO was applied and cycle length was 2000 ms. CaMK<sub>0</sub> for <svg height="11.9316pt" id="M115" style="vertical-align:-3.2957pt" version="1.1" viewbox="-0.0498162 -8.6359 20.6706 11.9316" width="20.6706pt" 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="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z" id="g113-74"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="428" vert-adv-y="428"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,4.719,3.132)"><path d="M618 181C565 77 513 26 413 26C264 26 151 150 151 336C151 486 240 625 407 625C516 625 573 582 600 475L634 483C627 540 622 581 613 638C585 643 518 665 435 665C211 665 46 526 46 315C46 158 157 -15 406 -15C480 -15 564 4 594 12C612 43 638 121 651 168L618 181Z" id="g58-65"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="673" vert-adv-y="673"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,10.926,3.132)"><path d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z" id="g58-95"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="449" vert-adv-y="449"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,15.011,3.132)"><path d="M499 166C484 119 466 88 447 68C424 43 390 38 338 38C297 38 262 40 242 51C223 62 218 80 218 133V522C218 607 226 612 309 617V650H41V617C124 612 131 605 131 522V129C131 45 123 38 38 33V0H497C505 30 529 128 534 160L499 166Z" id="g58-74"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="548" vert-adv-y="548"></glyph.data></g></svg> was 0.12 but CaMK<sub>0</sub> for other targets was 0.05. EADs occurred when <svg height="11.8174pt" id="M116" style="vertical-align:-3.1815pt" version="1.1" viewbox="-0.0498162 -8.6359 14.9892 11.8174" width="14.9892pt" 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="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z" id="g113-74"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="428" vert-adv-y="428"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,4.719,3.132)"><path d="M676 0V33C628 38 606 47 555 101S396 279 321 373C388 440 457 509 495 545C556 601 582 609 660 617V650H412V617L436 615C479 608 479 601 452 566C405 510 345 447 289 394C258 366 239 353 216 348V518C216 605 226 612 305 617V650H40V617C123 612 130 605 130 518V131C130 46 121 38 44 33V0H310V33C226 38 216 46 216 131V318C235 322 249 319 274 290C367 181 444 84 520 0H676Z" id="g58-73"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="685" vert-adv-y="685"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,10.879,3.132)"><path d="M185 344V453C137 433 92 421 41 413V386C100 378 104 375 104 310V106C104 41 97 35 33 30V0H268V30C190 35 185 41 185 107V283C206 340 240 371 267 371C282 371 296 364 310 351C316 344 325 343 336 348C357 357 369 378 369 399C369 424 345 451 310 451C262 451 219 397 187 344H185Z" id="g58-112"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="380" vert-adv-y="380"></glyph.data></g></svg> was blocked by 85% in (a), but when <svg height="11.8174pt" id="M117" style="vertical-align:-3.1815pt" version="1.1" viewbox="-0.0498162 -8.6359 14.9892 11.8174" width="14.9892pt" 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="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z" id="g113-74"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="428" vert-adv-y="428"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,4.719,3.132)"><path d="M676 0V33C628 38 606 47 555 101S396 279 321 373C388 440 457 509 495 545C556 601 582 609 660 617V650H412V617L436 615C479 608 479 601 452 566C405 510 345 447 289 394C258 366 239 353 216 348V518C216 605 226 612 305 617V650H40V617C123 612 130 605 130 518V131C130 46 121 38 44 33V0H310V33C226 38 216 46 216 131V318C235 322 249 319 274 290C367 181 444 84 520 0H676Z" id="g58-73"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="685" vert-adv-y="685"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,10.879,3.132)"><path d="M185 344V453C137 433 92 421 41 413V386C100 378 104 375 104 310V106C104 41 97 35 33 30V0H268V30C190 35 185 41 185 107V283C206 340 240 371 267 371C282 371 296 364 310 351C316 344 325 343 336 348C357 357 369 378 369 399C369 424 345 451 310 451C262 451 219 397 187 344H185Z" id="g58-112"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="380" vert-adv-y="380"></glyph.data></g></svg> blockage was reduced to 77%, EADs vanished in (c). (b) <svg height="11.9316pt" id="M118" style="vertical-align:-3.2957pt" version="1.1" viewbox="-0.0498162 -8.6359 20.6706 11.9316" width="20.6706pt" 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="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z" id="g113-74"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="428" vert-adv-y="428"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,4.719,3.132)"><path d="M618 181C565 77 513 26 413 26C264 26 151 150 151 336C151 486 240 625 407 625C516 625 573 582 600 475L634 483C627 540 622 581 613 638C585 643 518 665 435 665C211 665 46 526 46 315C46 158 157 -15 406 -15C480 -15 564 4 594 12C612 43 638 121 651 168L618 181Z" id="g58-65"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="673" vert-adv-y="673"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,10.926,3.132)"><path d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z" id="g58-95"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="449" vert-adv-y="449"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,15.011,3.132)"><path d="M499 166C484 119 466 88 447 68C424 43 390 38 338 38C297 38 262 40 242 51C223 62 218 80 218 133V522C218 607 226 612 309 617V650H41V617C124 612 131 605 131 522V129C131 45 123 38 38 33V0H497C505 30 529 128 534 160L499 166Z" id="g58-74"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="548" vert-adv-y="548"></glyph.data></g></svg> figures when EADs existed. (d) <svg height="11.9316pt" id="M119" style="vertical-align:-3.2957pt" version="1.1" viewbox="-0.0498162 -8.6359 20.6706 11.9316" width="20.6706pt" 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="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z" id="g113-74"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="428" vert-adv-y="428"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,4.719,3.132)"><path d="M618 181C565 77 513 26 413 26C264 26 151 150 151 336C151 486 240 625 407 625C516 625 573 582 600 475L634 483C627 540 622 581 613 638C585 643 518 665 435 665C211 665 46 526 46 315C46 158 157 -15 406 -15C480 -15 564 4 594 12C612 43 638 121 651 168L618 181Z" id="g58-65"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="673" vert-adv-y="673"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,10.926,3.132)"><path d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z" id="g58-95"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="449" vert-adv-y="449"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,15.011,3.132)"><path d="M499 166C484 119 466 88 447 68C424 43 390 38 338 38C297 38 262 40 242 51C223 62 218 80 218 133V522C218 607 226 612 309 617V650H41V617C124 612 131 605 131 522V129C131 45 123 38 38 33V0H497C505 30 529 128 534 160L499 166Z" id="g58-74"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="548" vert-adv-y="548"></glyph.data></g></svg> figures when EADs vanished.</div>

Computational and Mathematical Methods in Medicine

fig4

Figure 4

Figure 4: Role of CaMKII and PKA in Early Afterdepolarization of Human Ventricular Myocardium Cell: A Computational Model Study 