Isosteviol Sensitizes sarcK<sub>ATP</sub> Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes

<div>Sarc<svg height="11.5695pt" id="M50" style="vertical-align:-3.18152pt" version="1.1" viewbox="-0.0498162 -8.38798 26.1589 11.5695" width="26.1589pt" 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="M667 0V28C619 34 599 43 546 100C496 154 386 277 311 372C378 440 449 512 488 547C551 605 575 615 650 622V650H410V622L433 619C478 614 479 604 449 568C404 513 337 443 282 390C254 364 234 350 212 345V520C212 609 222 616 299 622V650H41V622C120 616 128 611 128 520V128C128 41 120 34 44 28V0H304V28C221 34 212 41 212 128V318C229 321 242 318 266 291C355 185 436 87 514 0H667Z" id="g121-73"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="673" vert-adv-y="673"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,8.749,3.132)"><path d="M682 0V33C615 38 603 49 571 134C507 305 441 494 378 665L343 655L136 136C101 48 86 41 22 33V0H246V33C170 41 161 50 183 112C196 152 209 192 224 232H441C461 176 478 126 493 87C504 49 499 41 433 33V0H682ZM425 279H242C273 363 303 448 335 533H337L425 279Z" id="g58-63"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="703" vert-adv-y="703"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,14.534,3.132)"><path d="M601 496C596 555 591 627 591 675H567C551 656 544 650 516 650H120C91 650 79 651 64 675H41C38 619 34 555 29 492H63C75 537 83 566 96 582C110 604 128 612 207 612H272V126C272 46 264 38 170 33V0H464V33C368 38 359 48 359 126V612H430C502 612 520 605 535 582C547 566 556 541 567 492L601 496Z" id="g58-82"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="628" vert-adv-y="628"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,20.249,3.132)"><path d="M46 650V618C122 613 130 611 130 522V128C130 46 123 40 40 32V0H319V32C227 40 217 42 217 128V279L292 260C303 259 322 258 338 261C436 272 534 337 534 467C534 534 508 580 469 609C428 640 371 650 299 650H46ZM217 558C217 585 220 596 228 603C235 610 256 615 284 615C367 615 435 571 435 463C435 339 358 304 291 304C256 304 229 310 217 317V558Z" id="g58-78"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="573" vert-adv-y="573"></glyph.data></g></svg> channel current was elicited by pinacidil and blocked by glibenclamide. (a) Representative whole-cell current traces of sarc<svg height="11.5695pt" id="M51" style="vertical-align:-3.18152pt" version="1.1" viewbox="-0.0498162 -8.38798 26.1589 11.5695" width="26.1589pt" 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="M667 0V28C619 34 599 43 546 100C496 154 386 277 311 372C378 440 449 512 488 547C551 605 575 615 650 622V650H410V622L433 619C478 614 479 604 449 568C404 513 337 443 282 390C254 364 234 350 212 345V520C212 609 222 616 299 622V650H41V622C120 616 128 611 128 520V128C128 41 120 34 44 28V0H304V28C221 34 212 41 212 128V318C229 321 242 318 266 291C355 185 436 87 514 0H667Z" id="g121-73"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="673" vert-adv-y="673"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,8.749,3.132)"><path d="M682 0V33C615 38 603 49 571 134C507 305 441 494 378 665L343 655L136 136C101 48 86 41 22 33V0H246V33C170 41 161 50 183 112C196 152 209 192 224 232H441C461 176 478 126 493 87C504 49 499 41 433 33V0H682ZM425 279H242C273 363 303 448 335 533H337L425 279Z" id="g58-63"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="703" vert-adv-y="703"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,14.534,3.132)"><path d="M601 496C596 555 591 627 591 675H567C551 656 544 650 516 650H120C91 650 79 651 64 675H41C38 619 34 555 29 492H63C75 537 83 566 96 582C110 604 128 612 207 612H272V126C272 46 264 38 170 33V0H464V33C368 38 359 48 359 126V612H430C502 612 520 605 535 582C547 566 556 541 567 492L601 496Z" id="g58-82"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="628" vert-adv-y="628"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,20.249,3.132)"><path d="M46 650V618C122 613 130 611 130 522V128C130 46 123 40 40 32V0H319V32C227 40 217 42 217 128V279L292 260C303 259 322 258 338 261C436 272 534 337 534 467C534 534 508 580 469 609C428 640 371 650 299 650H46ZM217 558C217 585 220 596 228 603C235 610 256 615 284 615C367 615 435 571 435 463C435 339 358 304 291 304C256 304 229 310 217 317V558Z" id="g58-78"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="573" vert-adv-y="573"></glyph.data></g></svg> channel without pinacidil (up), with 100 <i>μ</i>M pinacidil (middle) and with 10 <i>μ</i>M glibenclamide (bottom). (b) The representative time course of <svg height="11.5695pt" id="M52" style="vertical-align:-3.18152pt" version="1.1" viewbox="-0.0498162 -8.38798 26.1589 11.5695" width="26.1589pt" 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="M667 0V28C619 34 599 43 546 100C496 154 386 277 311 372C378 440 449 512 488 547C551 605 575 615 650 622V650H410V622L433 619C478 614 479 604 449 568C404 513 337 443 282 390C254 364 234 350 212 345V520C212 609 222 616 299 622V650H41V622C120 616 128 611 128 520V128C128 41 120 34 44 28V0H304V28C221 34 212 41 212 128V318C229 321 242 318 266 291C355 185 436 87 514 0H667Z" id="g121-73"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="673" vert-adv-y="673"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,8.749,3.132)"><path d="M682 0V33C615 38 603 49 571 134C507 305 441 494 378 665L343 655L136 136C101 48 86 41 22 33V0H246V33C170 41 161 50 183 112C196 152 209 192 224 232H441C461 176 478 126 493 87C504 49 499 41 433 33V0H682ZM425 279H242C273 363 303 448 335 533H337L425 279Z" id="g58-63"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="703" vert-adv-y="703"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,14.534,3.132)"><path d="M601 496C596 555 591 627 591 675H567C551 656 544 650 516 650H120C91 650 79 651 64 675H41C38 619 34 555 29 492H63C75 537 83 566 96 582C110 604 128 612 207 612H272V126C272 46 264 38 170 33V0H464V33C368 38 359 48 359 126V612H430C502 612 520 605 535 582C547 566 556 541 567 492L601 496Z" id="g58-82"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="628" vert-adv-y="628"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,20.249,3.132)"><path d="M46 650V618C122 613 130 611 130 522V128C130 46 123 40 40 32V0H319V32C227 40 217 42 217 128V279L292 260C303 259 322 258 338 261C436 272 534 337 534 467C534 534 508 580 469 609C428 640 371 650 299 650H46ZM217 558C217 585 220 596 228 603C235 610 256 615 284 615C367 615 435 571 435 463C435 339 358 304 291 304C256 304 229 310 217 317V558Z" id="g58-78"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="573" vert-adv-y="573"></glyph.data></g></svg> channel activation by pinacidil and inhibition by glibenclamide.</div>

Oxidative Medicine and Cellular Longevity

fig1

Figure 1

Figure 1: Isosteviol Sensitizes sarcK<sub>ATP</sub> Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes 

Figure 1 | Isosteviol Sensitizes sarcKATP Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes 