Baicalin, a flavonoid from Scutellaria baicalensis Georgi, activates large-conductance Ca²⁺-activated K⁺ channels via cyclic nucleotide-dependent protein kinases in mesenteric artery

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• 作者：Yi-Ling Lin ; Zen-Kong Dai ; Rong-Jyh Lin ; Koung-Shing Chu ; Ing-Jun Chen ; Jiunn-Ren Wu ; Bin-Nan Wu
• 关键词：Baicalin ; Mesenteric artery ; BK_Ca channels ; Patch clamp electrophysiology ; Protein kinases
• 刊名：Phytomedicine
• 出版年：2010
• 出版时间：August 2010
• 年：2010
• 卷：17
• 期：10
• 页码：760-770
• 全文大小：1015 K

文摘

Baicalin isolated from Scutellaria baicalensis is a traditional Chinese herbal medicine used for cardiovascular dysfunction. The ionic mechanism of the vasorelaxant effects of baicalin remains unclear. We investigated whether baicalin relaxes mesenteric arteries (MAs) via large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel activation and voltage-dependent Ca²⁺ channel (VDCC) inhibition. The contractility of MA was determined by dual wire myograph. BK_Ca channels and VDCCs were measured using whole-cell recordings in single myocytes, enzymatically dispersed from rat MAs. Baicalin (10-100 μM) attenuated 80 mM KCl-contracted MA in a concentration-related manner. L-NAME (30 μM) and indomethacin (10 μM) little affected baicalin (100 μM)-induced vasorelaxations. Contractions induced by iberiotoxin (IbTX, 0.1 μM), Bay K8644 (0.1 μM) or PMA (10 μM) were abolished by baicalin 100 μM. In MA myocytes, baicalin (0.3-30 μM) enhanced BK_Ca channel activity in a concentration-dependent manner. Increased BK_Ca currents were abolished by IbTX (0.1 μM). Baicalin-mediated (30 μM) BK_Ca current activation was significantly attenuated by an adenylate cyclase inhibitor (SQ 22536, 10 μM), a soluble guanylate cyclase inhibitor (ODQ, 10 μM), competitive antagonists of cAMP and cGMP (Rp-cAMP, 100 μM and Rp-cGMP, 100 μM), and cAMP- and cGMP-dependent protein kinase inhibitors (KT5720, 0.3 μM and KT5823, 0.3 μM). Perfusate with PMA (0.1 μM) abolished baicalin-enhanced BK_Ca currents. Additionally, baicalin (0.3-30 μM) reduced the amplitude of VDCC currents in a concentration-dependent manner and abolished VDCC activator Bay K8644-enhanced (0.1 μM) currents. Baicalin produced MA relaxation by activating BK_Ca and inhibiting VDCC channels by endothelium-independent mechanisms and by stimulating the cGMP/PKG and cAMP/PKA pathways.