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• W2759755230 abstract "Background and Purpose Ethanol at concentrations obtained in the circulation during moderate‐heavy episodic drinking (30–60 mM) causes cerebral artery constriction in several species, including humans. In rodents, ethanol‐induced cerebral artery constriction results from ethanol inhibition of large conductance voltage/Ca 2+ i ‐gated K + (BK) channels in cerebral artery myocytes. Moreover, the smooth muscle‐abundant BK β1 accessory subunit is required for ethanol to inhibit cerebral artery myocyte BK channels under physiological Ca 2+ i and voltages and thus constrict cerebral arteries. The molecular bases of these ethanol actions remain unknown. Here, we set to identify the BK β1 region(s) that mediates ethanol‐induced inhibition of cerebral artery myocyte BK channels and eventual arterial constriction. Experimental Approach We used protein biochemistry, patch‐clamp on engineered channel subunits, reversible cDNA permeabilization of KCNMB1 K/O mouse arteries and artery in vitro pressurization. Key Results Ethanol inhibition of BK current was facilitated by β1 but not β4 subunits. Furthermore, only BK complexes containing β chimeras with β1 transmembrane (TM) domains on a β4 background or with a β1 TM2 domain on a β4 background displayed ethanol responses identical to those of BK complexes including wild‐type β1. Moreover, β1 TM2 itself but not other β regions were necessary for ethanol‐induced cerebral artery constriction. Conclusions and Implications BK β1 TM2 is necessary for this subunit to enable ethanol‐induced inhibition of myocyte BK channels and cerebral artery constriction at physiological Ca 2+ and voltages. Thus, novel agents that target β1 TM2 may be considered to counteract ethanol‐induced cerebral artery constriction and associated cerebrovascular conditions." @default.
• W2759755230 created "2017-10-06" @default.
• W2759755230 creator A5005229667 @default.
• W2759755230 creator A5088744274 @default.
• W2759755230 date "2017-10-22" @default.
• W2759755230 modified "2023-10-14" @default.
• W2759755230 title "BK β1 subunit-dependent facilitation of ethanol inhibition of BK current and cerebral artery constriction is mediated by the β1 transmembrane domain 2" @default.
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• W2759755230 doi "https://doi.org/10.1111/bph.14046" @default.
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