Роль ионных каналов церебральных эндотелиоцитов в интегральной связи элементов гематоэнцефалического барьера (обзор)
Все анатомические элементы, которые входят в гематоэнцефалический барьер (ГЭБ), играют важную роль в регуляции проницаемости и гомеостаза ЦНС в норме и патологии. Этими элементами являются эндотелиальные клетки, перициты, астроглия и нейроны, и все они входят в понятие «нейроваскуляторная единица» (НВЕ). Будучи интеграционной системой, НВЕ тонко регулирует синаптическую пластичность нейронов, нейрогенез, межклеточные взаимодействия и проницаемость ГЭБ. Эндотелиальные клетки капилляров головного мозга являются важной составляющей НВЕ. В этом обзоре мы обсуждаем значительную роль эндотелиальных клеток капилляров мозга в поддержании структурной и функциональной целостности ГЭБ. В последние десятилетия большое внимание было уделено анализу экспрессии белков тесных контактов и белков адгезионных контактов в эндотелиальных клетках капилляров мозга и лишь относительно небольшое число исследований было сфокусировано на оценке экспрессии и функциональной активности ионных каналов в этих клетках, несмотря на то, что существует все большее число доказательств их важной роли в регуляции функций НВЕ/ГЭБ. В целом электрофизиологические свойства эндотелиальных клеток капилляров зависят от экспрессии различных ионных каналов, чья активность, по всей вероятности, координирует некоторые виды межклеточных взаимодействий в НВЕ и клетках артериол головного мозга. Мы остановили свое внимание на роли ионных каналов в регуляции активности клеток НВЕ, гладкомышечных клеток артериол и в модуляции локального кровотока головного мозга. Большое место в обзоре отведено лиганд-регулируемым ионным каналам, каналам, регулируемым внутриклеточными кальциевыми депо, TRP-каналам, кальций-активируемым и потенциалзависимым калиевым каналам в эндотелиальных клетках капилляров мозга и клетках артериол головного мозга. Понимание роли ионных каналов в контроле церебрального кровотока позволит определить новые терапевтические мишени для восстановления функциональной целостности НВЕ/ГЭБ при различных патологических состояниях (ишемия, нейровоспаление, нейродегенерация) in vivo и в моделях ГЭБ in vitro.
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