Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences67930910.31857/S0869813925020068UIRLJGEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch ArticleThe Contribution of BK Channels to Ischemic Reperfusion Changes in Cerebral Blood FlowВклад ВК-каналов в ишемически-реперфузионное нарушение кровотока в головном мозгеGorshkovaO. P.ГоршковаО. П.
Russian Federation
o_gorshkova@inbox.ruPavlov Institute of Physiology of the RASИнститут физиологии имени И.П. Павлова РАН16022025111227829009052025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/679309

Ischemic/reperfusion (I/R) damage of cerebral vessels is a complex dynamic process leading to hypoxic brain damage. To improve the outcome and treatment of the effects of I/R, an understanding of the molecular mechanisms of changes occurring in the cerebral vascular bed after recovery of blood flow is required in order to identify therapeutic intracellular targets. High-conductivity calcium-dependent potassium channels (BK) involved in the vasodilator reaction of cerebral vessels and highly sensitive to changes in oxygen levels can be considered as such targets. The work investigated the change in the contribution of BK channels to the rats pial arteries dilation after I/R. Using the method of in vivo vascular imaging in I/R and sham-operated rats, the number and degree of dilatation reactions in response to acetylcholine chloride (ACh, 10-7 M, 8 min) and exogenous hydrogen sulfide (H2S) donor sodium hydrosulfide (30 µM, 2 min) were compared before and after the use of the BK channel blocker tetraethylammonium chloride (2 mM, 5 min). It was found that I/R inhibit the dilatatory reaction. Changes in ACh-induced vasodilation persist for 21 days after I/R. Changes of H2S-mediated processes are noted only in the first 14 days and depend on the vessel size. These changes may be based on a gradually developing decrease in the contribution of BK channels to vasodilation, mainly expressed in large pial arteries. The decrease in the contribution of BK channels to dilation is most pronounced after 14 days and persists for 21 days after I/R.

Ишемически-реперфузионное (И/Р) повреждение церебральных сосудов – сложный динамический процесс, приводящий к гипоксическому повреждению головного мозга. Для улучшения исхода и лечения последствий И/Р требуется понимание молекулярных механизмов изменений, происходящих в мозговом сосудистом русле после восстановления кровотока, с целью выявления терапевтических внутриклеточных мишеней. В качестве таких мишеней могут быть рассмотрены кальций-зависимые калиевые каналы большой проводимости (ВК), обладающие высокой чувствительностью к гипоксии. В работе исследовано изменение вклада ВК-каналов в дилатацию пиальных артерий крыс после И/Р. С использованием метода видеомикроскопии сосудов у перенесших И/Р и ложнооперированных крыс сопоставлялись число и степень дилататорных реакций в ответ на воздействие ацетилхолин хлорида (АХ, 10-7 М, 8 мин) и донора экзогенного сероводорода (H2S) – гидросульфида натрия (30 мкМ, 2 мин) до и после блокады ВК-каналов хлоридом тетраэтиламмония (2 мМ, 5 мин). Обнаружено, что И/Р угнетает дилататорную реакцию. Изменения АХ-индуцированной вазодилатации сохраняются на протяжении 21 дня после И/Р. Нарушения H2S-опосредованных процессов отмечаются только в первые 14 дней и зависят от размера сосуда. В основе изменений вазодилатации может лежать постепенно развивающееся снижение вклада ВК-каналов, преимущественно выраженное на крупных пиальных артериях. Снижение вклада ВК каналов в дилатацию максимально выражено через 14 дней и сохраняется на протяжении 21 дня после И/Р.

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