Fenamates block gap junction coupling and potentiate BKCa channels in guinea pig arteriolar cells.
Fenamates block gap junction coupling and potentiate BKCa channels in guinea pig arteriolar cells.
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DOI：
10.1016/j.ejphar.2013.02.004
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发表时间：
2013-03-05
影响因子：
5
通讯作者：
Jiang, Zhi-Gen
中科院分区：
文献类型：
--
作者：
Li, Xin-Zhi;Ma, Ke-Tao;Guan, Bing-Cai;Li, Li;Zhao, Lei;Zhang, Zhong-Shuang;Si, Jun-Qiang;Jiang, Zhi-Gen
我们确定了fenamates，氟灭酸（FFA）和尼氟灭酸（NFA），对血管平滑肌细胞（VSMC）之间的间隙连接介导的细胞间耦合的急性分离的小动脉段从三个血管床：螺旋蜗轴动脉（SMA），小脑前下动脉（AICA）和肠系膜动脉（MA），并在分散的VSMC的非交界性膜通道的作用。使用常规的全细胞记录方法。FFA以浓度依赖性方式可逆地抑制SMA、AICA和MA段的输入电导（Ginput）或增加输入电阻（Rinput），其IC 50略有不同（分别为26、33和56 μM，P>0.05）。在≥300 μM时，记录的VSMC通常达到完全电绝缘。NFA对SMA、AICA和MA节段VSMCs之间的间隙连接具有相似的作用，IC 50分别为40、48和62 μM。FFA和NFA浓度依赖性地增加VSMCs的大电导钙激活钾通道（BKCa）介导的外向整流钾电流，其EC 50值均为300 μM左右。选择性阻断BKCa的伊比利亚毒素可抑制FFA和NFA对BKCa的增强作用。KV阻断剂4-AP对fenamate诱导的K+电流增强没有影响。我们的结论是，FFA和NFA阻断血管缝隙连接介导的电耦合均匀的三个血管床的小动脉，并在1000 μM的记录VSMC获得完全的电隔离; FFA和NFA还激活BKCa通道在小动脉平滑肌细胞除了其已知的抑制作用氯通道。
We determined the actions of the fenamates, flufenamic acid (FFA) and niflumic acid (NFA), on gap junction-mediated intercellular coupling between vascular smooth muscle cells (VSMC) in situ of acutely isolated arteriole segments from the three vascular beds: the spiral modiolar artery (SMA), anterior inferior cerebellar artery (AICA) and mesenteric artery (MA), and on non-junctional membrane channels in dispersed VSMCs. Conventional whole-cell recording methods were used. FFA reversibly suppressed the input conductance (Ginput) or increased the input resistance (Rinput) in a concentration dependent manner, with slightly different IC50s for the SMA, AICA and MA segments (26, 33 and 56 μM respectively, P>0.05). Complete electrical isolation of the recorded VSMC was normally reached at ≥300 μM. NFA had a similar effect on gap junction among VSMCs with an IC50 of 40, 48 and 62 μM in SMA, AICA and MA segments, respectively. In dispersed VSMCs, FFA and NFA increased outward rectifier K+-current mediated by the big conductance calcium-activated potassium channel (BKCa) in a concentration-dependent manner, with a similar EC50 of ~300 μM for both FFA and NFA in the three vessels. Iberiotoxin, a selective blocker of the BKCa, suppressed the enhancement of the BKCa by FFA and NFA. The KV blocker 4-AP had no effect on the fenamates-induced K+-current enhancement. We conclude that FFA and NFA blocked the vascular gap junction mediated electrical couplings uniformly in arterioles of the three vascular beds, and complete electrical isolation of the recorded VSMC is obtained at ≧300 μM; FFA and NFA also activate BKCa channels in the arteriolar smooth muscle cells in addition to their known inhibitory effects on chloride channels.
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影响因子：
5.5
作者：
Saleh, S. N.;Albert, A. P.;Large, W. A.
通讯作者：
Large, W. A.
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Beech, DJ
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作者：
Jung, S;Strotmann, R;Plant, TD
通讯作者：
Plant, TD