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

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-mediated 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.