Functional effects of KCNQ K(+) channels in airway smooth muscle.
Functional effects of KCNQ K(+) channels in airway smooth muscle.
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DOI：
10.3389/fphys.2013.00277
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发表时间：
2013
影响因子：
4
通讯作者：
Brenner R
中科院分区：
文献类型：
--
作者：
Evseev AI;Semenov I;Archer CR;Medina JL;Dube PH;Shapiro MS;Brenner R
KCNQ (Kv7) 通道是电压门控 K+ 电流的基础，该电流最出名的是控制神经元兴奋性及其通过 Gq/11 耦合毒蕈碱信号传导的抑制。研究表明 KCNQ 通道在气道平滑肌 (ASM) 中表达，该组织主要受毒蕈碱受体信号传导调节。因此，我们研究了啮齿动物 ASM 中 KCNQ 通道的功能及其与 Gq/11 偶联 M3 毒蕈碱受体的相互作用。分离的 ASM 细胞的穿孔膜片钳检测到 K+ 电流被 KCNQ 拮抗剂 XE991 抑制，并被特定激动剂氟吡汀增强。 KCNQ 通道在 ASM 细胞静息电位附近的电压下开始激活，并且 XE991 确实使静息膜电位去极化。毒蕈碱受体激活在收缩最大浓度的一半时微弱地抑制 KCNQ 电流（约 20%）。因此，我们惊讶地发现 KCNQ 对毒蕈碱激活后的膜电压或肌肉收缩力没有影响。此外，单独的 M3 受体特异性拮抗剂 J104129 富马酸盐并未揭示 KCNQ 对毒蕈碱诱发的去极化或收缩性的影响。然而，当 BK-K+ 通道活动减少时，KCNQ 通道的作用就会显现出来。虽然 KCNQ 通道确实控制静息电位，但它们似乎在 ASM 毒蕈碱信号传导过程中与 BK 钙激活 K+ 通道一起发挥冗余作用。与拮抗剂的作用相反，我们观察到 KCNQ 激动剂氟吡汀在体外引起显着的超极化并减少收缩，无论毒蕈碱激活如何。使用非侵入性整体动物体积描记法，临床批准的 KCNQ 激动剂瑞替加滨可导致接受毒蕈碱激动剂治疗的野生型和 BK β1 敲除 (KO) 小鼠的气道阻力指数短暂降低。这些发现表明，KCNQ 通道可以通过激动剂招募来对抗毒蕈碱诱发的收缩，并且可能具有作为支气管扩张剂的治疗价值。
KCNQ (Kv7) channels underlie a voltage-gated K+ current best known for control of neuronal excitability, and its inhibition by Gq/11-coupled, muscarinic signaling. Studies have indicated expression of KCNQ channels in airway smooth muscle (ASM), a tissue that is predominantly regulated by muscarinic receptor signaling. Therefore, we investigated the function of KCNQ channels in rodent ASM and their interplay with Gq/11-coupled M3 muscarinic receptors. Perforated-patch clamp of dissociated ASM cells detected a K+ current inhibited by the KCNQ antagonist, XE991, and augmented by the specific agonist, flupirtine. KCNQ channels begin to activate at voltages near resting potentials for ASM cells, and indeed XE991 depolarized resting membrane potentials. Muscarinic receptor activation inhibited KCNQ current weakly (~20%) at concentrations half-maximal for contractions. Thus, we were surprised to see that KCNQ had no affect on membrane voltage or muscle contractility following muscarinic activation. Further, M3 receptor-specific antagonist J104129 fumarate alone did not reveal KCNQ effects on muscarinic evoked depolarization or contractility. However, a role for KCNQ channels was revealed when BK-K+ channel activities are reduced. While KCNQ channels do control resting potentials, they appear to play a redundant role with BK calcium-activated K+ channels during ASM muscarinic signaling. In contrast to effect of antagonist, we observe that KCNQ agonist flupirtine caused a significant hyperpolarization and reduced contraction in vitro irrespective of muscarinic activation. Using non-invasive whole animal plethysmography, the clinically approved KCNQ agonist retigabine caused a transient reduction in indexes of airway resistance in both wild type and BK β1 knockout (KO) mice treated with the muscarinic agonist. These findings indicate that KCNQ channels can be recruited via agonists to oppose muscarinic evoked contractions and may be of therapeutic value as bronchodilators.
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影响因子：
3.5
作者：
Mitsuya, M;Mase, T;Tomimoto, K
通讯作者：
Tomimoto, K
大鼠海马中M通道亚基KCNQ2和KCNQ3的分布。
影响因子：
5.7
作者：
Klinger, Felicia;Gould, Georgianna;Boehm, Stefan;Shapiro, Mark S.
通讯作者：
Shapiro, Mark S.
DOI：
10.1016/j.juro.2009.02.108
发表时间：
2009-07
期刊：
The Journal of urology
影响因子：
--
作者：
Anderson UA;Carson C;McCloskey KD
通讯作者：
McCloskey KD
影响因子：
--
作者：
Lomask, Morton
通讯作者：
Lomask, Morton
DOI：
10.1007/978-1-60761-500-2_26
发表时间：
2010-01-01
期刊：
MEMBRANE RECEPTORS, CHANNELS AND TRANSPORTERS IN PULMONARY CIRCULATION
影响因子：
--
作者：
Gurney, Alison M.;Joshi, Shreena;Manoury, Boris
通讯作者：
Manoury, Boris