Opposing roles of smooth muscle BK channels and ryanodine receptors in the regulation of nerve-evoked constriction of mesenteric resistance arteries
Opposing roles of smooth muscle BK channels and ryanodine receptors in the regulation of nerve-evoked constriction of mesenteric resistance arteries
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DOI：
10.1152/ajpheart.00866.2013
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发表时间：
2014-04-01
影响因子：
4.8
通讯作者：
Nelson, Mark T.
中科院分区：
文献类型：
--
作者：
Krishnamoorthy, Gayathri;Sonkusare, Swapnil K.;Nelson, Mark T.
在受压脑动脉的去极化平滑肌细胞中，兰尼碱受体 (RyR) 产生“Ca2+ 火花”，激活大电导、Ca2+- 和电压敏感钾 (BK) 通道，以对抗压力引起的（肌源性）收缩。在这里，我们发现 BK 通道和 RyR 在响应电场刺激交感神经激活的动脉张力调节中具有相反的作用。用桩碱抑制 BK 通道会增加小鼠受压、阻力大小的肠系膜动脉的肌源性和神经性收缩。用兰尼碱抑制 RyRs 会增加肌原性收缩，但会减少神经诱发的收缩，同时降低神经诱发的细胞内 Ca2+ 增加幅度。在存在 L 型电压依赖性 Ca2+ 通道 (VDCC) 拮抗剂的情况下，神经刺激无法引起动脉直径的变化，而 BK 通道和 RyR 抑制剂则没有效果，这表明神经诱导的收缩依赖于 VDCC 的激活。总的来说，这些结果表明 BK 通道和 RyR 在肌源性与神经源性张力的调节中具有不同的作用：虽然 BK 通道和 RyR 协同作用以对抗肌源性血管收缩，但 BK 通道对抗神经源性血管收缩而 RyR 增强它。提出了一种神经源性血管调节方案，其中 RyR 与 VDCC 联合作用，调节肠系膜阻力动脉中神经诱发的收缩。
In depolarized smooth muscle cells of pressurized cerebral arteries, ryanodine receptors (RyRs) generate "Ca2+ sparks" that activate large-conductance, Ca2+-, and voltage-sensitive potassium (BK) channels to oppose pressure-induced (myogenic) constriction. Here, we show that BK channels and RyRs have opposing roles in the regulation of arterial tone in response to sympathetic nerve activation by electrical field stimulation. Inhibition of BK channels with paxilline increased both myogenic and nerve-induced constrictions of pressurized, resistance-sized mesenteric arteries from mice. Inhibition of RyRs with ryanodine increased myogenic constriction, but it decreased nerve-evoked constriction along with a reduction in the amplitude of nerve-evoked increases in global intracellular Ca2+. In the presence of L-type voltage-dependent Ca2+ channel (VDCC) antagonists, nerve stimulation failed to evoke a change in arterial diameter, and BK channel and RyR inhibitors were without effect, suggesting that nerve-induced constriction is dependent on activation of VDCCs. Collectively, these results indicate that BK channels and RyRs have different roles in the regulation of myogenic versus neurogenic tone: whereas BK channels and RyRs act in concert to oppose myogenic vasoconstriction, BK channels oppose neurogenic vasoconstriction and RyRs augment it. A scheme for neurogenic vasoregulation is proposed in which RyRs act in conjunction with VDCCs to regulate nerve-evoked constriction in mesenteric resistance arteries.