Калиевые каналы семейства Кv7 – новая мишень лечения нейродегенеративных нарушений
Ключевые слова:
эпилепсия, калиевые каналы, аксон, деполяризация, фосфатидилинозитол-4,5- бисфосфат, кальмодулин, синапс, ретигабинАннотация
Калиевые каналы принимают участие в формировании возбудимости нейрона при эпилепсии наравне
с другими каналами, но их роль была практически не исследованной. В нервной системе роль тормозных
калиевых каналов часто недооценивается, поскольку им трудно приписать какую-нибудь простую, интуитивно
понятную функцию, в отличие от, например, деполяризующих каналов, открытие которых приводит к
возникновению потенциалов действия и далее к передаче электрического сигнала на мышцу и ее сокращению.
Тем не менее уже сейчас ясно, что калиевые каналы незримо принимают участие практически в каждом
проявлении работы мозга, в каждом его нейроне, и их вклад становится особенно заметен при изучении таких
экстремальных состояний, как эпилепсия. Потенциал-чувствительные каналы Kv7.2/3 обеспечивают
неинактивируемый калиевый M-ток, который регулирует потенциал покоя нейрона в компартментспецифической манере. Это означает, что сами каналы Kv7.2/3 локализуются в аксоне нейрона и там
активируются.
Каналы Kv7 уникальны среди каналов K+
, поскольку четыре из пяти подтипов каналов играют хорошо
документированную роль в развитии заболеваний человека. Они выполняют различные физиологические
функции в сердце и нервной системе, что можно объяснить их свойствами управления потенциалом. Каналы
Kv7 также поддаются фармакологической модуляции, а синтетические открыватели и блокаторы каналов,
регулирующие нейронную возбудимость, существовали еще до того, как каналы Kv7 были идентифицированы
путем клонирования. В этом обзоре мы обсудим общую характеристику каналов Kv7 за последние годы,
историю открытия, структуру субъединиц Kv7, физиологию в нормальных и патологических условиях
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