The Contribution of BK Channels to Ischemic/Reperfusion Changes in Cerebral Blood Flow

Ischemic/reperfusion (I/R) damage of cerebral vessels is acomplex dynamic process leading to hypoxic brain damage. To improvethe outcome and treatment of the effects of I/R, an understandingof the molecular mechanisms of changes occurring in the cerebralvascular bed after recovery of blood flow is required in order toidentify therapeutic intracellular targets. High-conductivity calcium-dependent potassiumchannels (BK) involved in the vasodilator reaction of cerebral vesselsand highly sensitive to changes in oxygen levels can be consideredas such targets. The work investigated the change in the contributionof BK channels to the rats pial arteries dilation after I/R. Usingthe method of in vivo vascular imaging in I/R and sham-operatedrats, the number and degree of dilatation reactions in responseto acetylcholine chloride (ACh, 10^–7 M,8 min) and exogenous hydrogen sulfide (H₂S)donor sodium hydrosulfide (30 µM, 2 min) were compared before andafter the use of the BK channel blocker tetraethylammonium chloride(2 mM, 5 min). It was found that I/R inhibit the dilatatory reaction. Changesin ACh-mediated vasodilation persist for 21 days after I/R. Changesof H₂S–mediated processes are noted onlyin the first 14 days and depend on the vessel size. These changesmay be based on a gradually developing decrease in the contributionof BK channels to vasodilation, mainly expressed in large pial arteries.The decrease in the contribution of BK channels to dilation is mostpronounced after 14 days and persists for 21 days after I/R.