ЗАКЛЮЧЕНИЕ. 1. Дано дальнейшее развитие электронно-конформационной модели RyR-канала и кластера RyR-каналов на мембране саркоплазматического ретикулюма в высвобождающей

ОСНОВНЫЕ РЕЗУЛЬТАТЫ И ВЫВОДЫ

1. Дано дальнейшее развитие электронно-конформационной модели RyR-канала и кластера RyR-каналов на мембране саркоплазматического ретикулюма в высвобождающей единице. Впервые в ЭК-модели предложено введение дополнительного, инактивационного состояния. Предложена новая модель взаимодействия ионов Са²⁺ с активационным центром RyR-канала, учитывающая вероятности заполнения мест присоединения активационного центра ионами Са²⁺. Дана детализация модели туннельных переходов, включающая введение «зоны разрешенного туннельного перехода» вблизи минимума конформационного потенциала RyR-канала.

2. Разработан многоцелевой компьютерный комплекс, реализующий алгоритмы численного решения уравнений электронно-конформационной модели и единой модели Са²⁺ высвобождающей единицы, на базе которого проводились серии экспериментов по изучению динамики одиночного RyR-канала, кластера RyR-каналов и Са²⁺ высвобождающей единицы.

3. Впервые в рамках электронно-конформационной модели воспроизведены и объяснены основные экспериментально наблюдаемые особенности функционирования одиночного RyR-канала:

- экстремальная зависимость вероятности пребывания RyR-канала в открытом состоянии от концентрации Са²⁺;

- влияние ионов Mg²⁺ на процесс активации RyR-канала;

- эффект адаптации RyR-канала к продолжительной стимуляции.

4. Разработана единая модель Са²⁺ высвобождающей единицы, объединяющая электронно-конформационную модель функционирования кластера RyR-каналов с моделью динамики ионов Са²⁺ между отделами высвобождающей единицы.

5. Впервые в рамках ЭК-модели исследована изолированная Са²⁺ высвобождающая единица в клетках водителя сердечного ритма (Ca²⁺-«часы»). Численные эксперименты показали, что изолированная ВЕ в широком диапазоне параметров может вести себя как самоподдерживающийся кальциевый осциллятор. Выявлена различные режимы функционирования изолированной ВЕ. Отмечено, что в физиологическом режиме при повышении частоты увеличивается амплитуда осцилляций Са²⁺-«часов», что на молекулярном уровне объясняет принцип Боудича «чаще-сильнее» работы сердечных клеток.

7. Впервые исследовано влияние взаимодействия между RyR-каналами на стабильность работы Са²⁺-«часов». Показано, что включение конформационного взаимодействия между каналами приводит к стабилизации осцилляций по частоте и амплитуде.

8. Впервые обнаружен и исследован эффект случайной остановки осцилляций Са²⁺-«часов» при достаточно сильном взаимодействии между RyR-каналами в ВЕ.

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