Abstract P163: Acute Treatment With Amyloid Beta Impaired Cerebral Artery Reactivity And Endothelial Sk Channel Activity

Introduction: The accumulation/aggregation of amyloid-beta(Aβ) has been recognized to play a key role in the progression of Alzheimer’s disease (AD) and the neurovascular dysfunction induced by Aβ may contribute to cognitive impairment and dementia during AD. Aβ deposition in cerebrovasculature exerts direct toxicity to smooth muscle cells and impairs nitric oxide signaling in the endothelium. Endothelium-dependent hyperpolarization and vascular relaxation are partially mediated by small-conductance calcium-activated potassium (SK) channels, and the inhibition of SK channels plays an important role in endothelial dysfunction. However, there has been limited investigation into the acute effect of Aβ on the endothelial SK channel function and related cerebrovascular reactivity. Hypothesis: We hypothesized that acute treatment with Aβ downregulates SK channel activity and impaired cerebrovascular reactivity. Methods: Aβ and SK channel activator NS309 were used in measuring in-vitro relaxation response of pre-contracted mouse cerebral arteries, and the SK channel currents of human cerebral artery endothelial cells by the whole-cell patch-clamp. Results: Mouse cerebral artery diameter was no significantly changed in incubation with Aβ (0.5-5μM) for 5 minutes (Fig. A, n=6, respectively). However, cerebral artery dilation with NS309 (10μM) was significantly decreased after incubation with Aβ (1μM) for 2 hours (Fig. B, n=6, respectively). The patch clamp recording showed that total potassium currents were no significantly changed in the incubation with Aβ (0.5-5μM) for 5 minutes (Fig. C&D, n=6, respectively). In contrast, the currents of SK channels in cerebral artery endothelial cells were significantly impaired after incubation with Aβ (1μM) for 2 hours (Fig. E&F, n=5-7, respectively). Conclusions: Acute treatment with Aβ dysregulated of cerebrovascular endothelial SK channels and impaired the cerebrovascular reactivity.