Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal K<sup>+</sup>-Cl<sup>-</sup> Cotransporter KCC2

<p><svg height="11.9218pt" id="M18" style="vertical-align:-3.181499pt" version="1.1" viewbox="-0.0498162 -8.7403 42.8888 11.9218" width="42.8888pt" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M703 311H403V276C508 267 513 259 513 189V94C513 63 505 47 490 38C477 29 454 26 434 26C270 26 196 184 196 335C196 515 300 623 420 623C514 623 589 576 613 464L651 472C643 550 638 603 635 637C599 645 522 665 440 665C229 665 44 546 44 318C44 117 193 -15 425 -15C506 -15 593 7 653 21C648 47 647 79 647 115V195C647 262 653 266 703 276V311Z"></path></g><g transform="matrix(.013,0,0,-0.013,9.451,0)"><path d="M687 0V35C623 43 611 56 577 144C512 316 450 490 386 665L335 652L130 138C97 54 84 43 18 35V0H242V35C169 44 166 58 181 106C193 146 206 182 217 213H409C424 173 439 130 449 100C465 56 460 44 401 35V0H687ZM390 266H234C260 337 285 410 313 483H316L390 266Z"></path></g><g transform="matrix(.013,0,0,-0.013,18.629,0)"><path d="M401 353C473 367 557 406 557 502C557 551 535 592 498 616C460 640 410 650 333 650H41V615C112 608 121 602 121 516V134C121 49 112 42 35 35V0H289C372 0 449 14 500 43C556 74 593 126 593 193C593 288 517 335 401 349V353ZM253 363V553C253 574 255 589 262 596C268 602 284 609 307 609C361 609 415 575 415 484C415 401 372 363 276 363H253ZM253 323H273C386 323 445 276 445 182C445 84 382 43 326 42C273 41 253 62 253 136V323Z"></path></g><g transform="matrix(.013,0,0,-0.013,26.401,0)"><path d="M687 0V35C623 43 611 56 577 144C512 316 450 490 386 665L335 652L130 138C97 54 84 43 18 35V0H242V35C169 44 166 58 181 106C193 146 206 182 217 213H409C424 173 439 130 449 100C465 56 460 44 401 35V0H687ZM390 266H234C260 337 285 410 313 483H316L390 266Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,35.579,3.132)"><path d="M698 0V42C632 50 620 61 587 147C521 317 460 491 396 665L338 652L135 141C103 59 91 50 23 42V0H252V42C181 50 179 63 192 108C204 146 216 179 225 206H418C432 170 446 131 456 102C471 60 465 50 409 42V0H698ZM398 265H244C270 336 294 407 321 478H324L398 265Z"></path></g></svg><b> signalling shifts from depolarizing to hyperpolarising responses during development</b>. In immature pyramidal cells, <svg height="11.9479pt" id="M19" style="vertical-align:-3.181499pt" version="1.1" viewbox="-0.0498162 -8.7664 41.7418 11.9479" width="41.7418pt" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M692 302H438V274C537 267 543 260 543 188V103C543 61 531 48 511 37C489 26 458 20 424 20C231 20 146 188 146 333C146 517 258 630 411 630C507 630 582 597 606 474L634 480C627 546 622 601 619 636C586 643 510 665 426 665C230 665 44 552 44 321C44 122 191 -15 411 -15C491 -15 573 7 635 21C629 49 628 81 628 116V202C628 261 632 266 692 274V302Z"></path></g><g transform="matrix(.013,0,0,-0.013,9.295,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"></path></g><g transform="matrix(.013,0,0,-0.013,18.278,0)"><path d="M372 352C427 368 507 407 507 502C507 548 486 592 451 616C420 638 376 650 301 650H44V622C124 616 128 610 128 527V123C128 40 122 34 36 28V0H257C336 0 402 12 453 40C512 72 548 124 548 191C548 291 471 335 372 350V352ZM213 362V558C213 591 216 602 226 608C235 614 258 618 282 618C377 618 415 558 415 490C415 406 369 362 260 362H213ZM213 328H258C380 328 450 283 450 181C450 76 377 35 296 34C231 34 213 53 213 125V328Z"></path></g><g transform="matrix(.013,0,0,-0.013,25.609,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,34.592,3.132)"><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"></path></g></svg>R-mediated Cl<sup>−</sup> currents are outward and depolarising because the relative ratio of NKCC1 to KCC2 activity is high. In mature neurons, increased KCC2 activity gives rise to inward <span class="nowrap"><svg height="11.9479pt" id="M20" style="vertical-align:-3.181499pt" version="1.1" viewbox="-0.0498162 -8.7664 41.7418 11.9479" width="41.7418pt" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M692 302H438V274C537 267 543 260 543 188V103C543 61 531 48 511 37C489 26 458 20 424 20C231 20 146 188 146 333C146 517 258 630 411 630C507 630 582 597 606 474L634 480C627 546 622 601 619 636C586 643 510 665 426 665C230 665 44 552 44 321C44 122 191 -15 411 -15C491 -15 573 7 635 21C629 49 628 81 628 116V202C628 261 632 266 692 274V302Z"></path></g><g transform="matrix(.013,0,0,-0.013,9.295,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"></path></g><g transform="matrix(.013,0,0,-0.013,18.278,0)"><path d="M372 352C427 368 507 407 507 502C507 548 486 592 451 616C420 638 376 650 301 650H44V622C124 616 128 610 128 527V123C128 40 122 34 36 28V0H257C336 0 402 12 453 40C512 72 548 124 548 191C548 291 471 335 372 350V352ZM213 362V558C213 591 216 602 226 608C235 614 258 618 282 618C377 618 415 558 415 490C415 406 369 362 260 362H213ZM213 328H258C380 328 450 283 450 181C450 76 377 35 296 34C231 34 213 53 213 125V328Z"></path></g><g transform="matrix(.013,0,0,-0.013,25.609,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,34.592,3.132)"><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"></path></g></svg>-</span>mediated Cl<sup>−</sup> currents that hyperpolarize the membrane potential.</p>

BioMed Research International

fig1

Figure 1

Figure 1: Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal K<sup>+</sup>-Cl<sup>-</sup> Cotransporter KCC2 

BioMed Research International

Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal K+-Cl- Cotransporter KCC2

Figure 1

Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal K⁺-Cl^- Cotransporter KCC2