Ккончание пресинаптического нейрона

Чтобы понять, как найти способ восстанавливать холинэргическую передачу импульсов только там, где это необходимо, рассмотрим «жизненный цикл» молекулы ацетилхолина. Этот медиатор производится в основном прямо в тех нервных окончаниях, из которых он затем и выделяется. Первый этап его синтеза — поглощение холина из синаптической щели (узкого пространства между окончанием пресинаптического нейрона, откуда выделяется медиатор, когда до этой клетки доходит нервный импульс, и поверхностью постсинаптического нейрона, попав на которую медиатор оказывает свое действие, изменяя электрическую активность принимающего импульс нейрона). Холин попадает внутрь окончания с помощью любого из двух транспортных белков, имеющихся в мембране пресинаптической клетки. Один из них присутствует не только в холинэргнческих нейронах, но и во всех других клетках, так как холин необходим для синтеза фосфатидилхолина, или лецитина — компонента клеточных мембран. Другой транспортный белок обнаружен только на холинэргических окончаниях; он обладает очень высоким сродством к холину, так что окончание поглощает холин из синаптической щели до тех пор, пока его там почти совсем не остается.

На следующем этапе, катализируемом ХАТ, холин реагирует с ацетилко- ферментом А и образуется ацетнлхолин. Нервные окончания содержат ХАТ в избытке, а предшественники (холин и ацетилкофермент А) — в количестве слишком малом, чтобы занять все молекулы фермента полностью; таким образом, скорость синтеза медиатора ограничена уровнем не фермента, а предшественников. Синтезированные молекулы ацетилхолина хранятся в окончании нейрона до тех пор, пока в него не поступит нервный импульс, который вызывает выход части из них в синаптическую щель. Попав туда, эти молекулы, во-первых, могут вступить во взаимодействие с рецепторами, находящимися на постсинаптическом нейроне, и тем самым передать сигнал, принесенный нервным импульсом. Во-вторых, ацетилхолин расщепляется ферментом ацетилхолинэстеразой, давая холин. В третьих, он может связаться с рецептором на пресннаптической мембране, откуда он секретировался, подавая таким образом сигнал, который модулирует последующее выделение ацетилхолина из окончания.

Каждый из этих этапов «жизненного цикла» молекулы ацетилхолина предоставляет нейрофармакологу поле деятельности для воздействия лекарством.

 

 

 

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