Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5-bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries
Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5-bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries
复制标题
大鼠肠系膜动脉 KCNQ 通道的磷脂酰肌醇-4,5-二磷酸依赖性调节促进交感神经传递
作者：
Yasuo Kansui;K. Goto;T. Ohtsubo;Noboru Murakami;K. Ichishima;K. Matsumura;T. Kitazono
交感神经通过向血管系统释放神经递质来调节血管张力。我们先前证明缓激肽促进大鼠肠系膜动脉的交感神经传递。尽管对这种神经传递的细胞内调控机制知之甚少，但最近的细胞系实验表明，KCNQ通道参与了缓激肽对神经传递的调控，该通道被膜磷脂酰肌醇-4，5-二磷酸(PIP2)的耗竭所抑制。在本研究中，我们研究了大鼠血管周围交感神经递质释放的调节机制。用常规微电极技术记录大鼠肠系膜动脉重复刺激(1 Hz，11次，20 μS，20~50 V)诱发的兴奋性连接电位(EjPs)。缓激肽(10−7 L−1)可显著增强EjP波幅(n=2 2，P<0.0 5)。这种增强作用可被ω-芋螺毒素GVIA(2×10−9 L−1，n=8)抑制N型钙通道所阻断。用U-73122(10−6 L−1，n=17)阻断磷脂酶C也可消除缓激肽的易化作用。此外，用Wortmannin(10−5 L−1，n=7)或用XE-991(10−5 ol L−1，n=7)抑制KCNQ通道，均可减弱缓激肽的作用。而用环匹阿松酸(3×10−6 L−1，n=6)耗竭细胞内钙库，或用双吲哚马来酰亚胺I(10−6 m ol L−1，n=9)抑制蛋白激酶C，均不改变缓激肽的作用。这些结果表明，由GQ/11偶联受体激活的磷脂酶C对PIP2的水解以及随后的KCNQ通道抑制可能通过激活大鼠肠系膜动脉的N型钙通道来增强交感神经递质。
Sympathetic nerves regulate vascular tone by releasing neurotransmitters into the vasculature. We previously demonstrated that bradykinin facilitates sympathetic neurotransmission in rat mesenteric arteries. Although little is known about the intracellular mechanism modulating this neurotransmission, recent cell line experiments have shown that the KCNQ channel, which is inhibited by the depletion of membrane phosphatidylinositol-4,5-bisphosphate (PIP2), participates in the control of neurotransmission by bradykinin. In the present study, we examined the mechanism regulating neurotransmitter release from rat perivascular sympathetic nerves. Excitatory junction potentials (EJPs) elicited by repetitive nerve stimulation (1 Hz, 11 pulses, 20 μs, 20–50 V), a measure of sympathetic purinergic neurotransmission, were recorded with a conventional microelectrode technique in rat mesenteric arteries. Bradykinin (10−7 mol l−1) significantly enhanced the amplitude of EJPs (n=22, P<0.05). This enhancing effect was abolished by N-type calcium-channel inhibition with ω-conotoxin GVIA (2 × 10−9 mol l−1, n=8). The blockade of phospholipase C with U-73122 (10−6 mol l−1, n=17) also eliminated the facilitatory effect of bradykinin. In addition, the effects of bradykinin were diminished by the prevention of PIP2 resynthesis with wortmannin (10−5 mol l−1 n=7) or KCNQ channel inhibition with XE-991 (10−5 mol l−1, n=7). On the other hand, depletion of intracellular calcium stores with cyclopiazonic acid (3 × 10−6 mol l−1, n=6) or the inhibition of protein kinase C with bisindolylmaleimide-I (10−6 mol l−1, n=9) did not alter the action of bradykinin. These data demonstrate that the hydrolysis of PIP2 by phospholipase C, which is activated by Gq/11-coupled receptors, and subsequent KCNQ channel inhibition enhance sympathetic purinergic neurotransmission presumably via the activation of N-type calcium channels in rat mesenteric arteries.
影响因子：
21.1
作者：
S. H. Buck;T. Burks
通讯作者：
S. H. Buck;T. Burks
DOI：
--
发表时间：
1999-08
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
N. Seyedi;R. Maruyama;R. Levi
通讯作者：
N. Seyedi;R. Maruyama;R. Levi
影响因子：
37.8
作者：
Jepps, Thomas A.;Chadha, Preet S.;Greenwood, Iain A.
通讯作者：
Greenwood, Iain A.