Enhanced β-adrenergic response in mice with dominant-negative expression of the PKD2L1 channel.
Enhanced β-adrenergic response in mice with dominant-negative expression of the PKD2L1 channel.
复制标题
DOI：
10.1371/journal.pone.0261668
复制
发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Miyoshi I
中科院分区：
文献类型：
--
作者：
Murakami M;Murakami AM;Nemoto T;Ohba T;Yonekura M;Toyama Y;Tomita H;Matsuzaki Y;Sawamura D;Hirota K;Itagaki S;Asada Y;Miyoshi I
多囊肾病（PKD）是人类肾衰竭最常见的遗传原因。在各种pkd相关分子中，PKD2L1形成阳离子通道，但其生理重要性尚不清楚。在本研究中，我们通过过表达小鼠PKD2L1基因的显性阴性形式（即缺乏成孔结构域）建立了转基因小鼠系。由此产生的PKD2L1del-Tg小鼠表现出室上过早收缩，对β-肾上腺素能刺激的敏感性增强，心电图R-R间期不稳定。自发心房收缩时，PKD2L1del-Tg心房对异丙肾上腺素、去甲肾上腺素和肾上腺素的敏感性增强。动作电位记录显示异丙肾上腺素对PKD2L1del-Tg心房的动作电位持续时间缩短。这些发现表明PKD2L1 - tg小鼠肾上腺素能敏感性增加，表明PKD2L1参与交感调节。
Polycystic kidney disease (PKD) is the most common genetic cause of kidney failure in humans. Among the various PKD-related molecules, PKD2L1 forms cation channels, but its physiological importance is obscure. In the present study, we established a transgenic mouse line by overexpressing the dominant-negative form of the mouse PKD2L1 gene (i.e., lacking the pore-forming domain). The resulting PKD2L1del-Tg mice exhibited supraventricular premature contraction, as well as enhanced sensitivity to β-adrenergic stimulation and unstable R-R intervals in electrocardiography. During spontaneous atrial contraction, PKD2L1del-Tg atria showed enhanced sensitivity to isoproterenol, norepinephrine, and epinephrine. Action potential recording revealed a shortened action potential duration in PKD2L1del-Tg atria in response to isoproterenol. These findings indicated increased adrenergic sensitivity in PKD2L1del-Tg mice, suggesting that PKD2L1 is involved in sympathetic regulation.
登录
查看更多内容
影响因子：
56.9
作者：
Mochizuki, T;Wu, GQ;Somlo, S
通讯作者：
Somlo, S
影响因子：
13.6
作者：
Basora, N;Nomura, H;Zhou, J
通讯作者：
Zhou, J
DOI：
10.1073/pnas.081089398
发表时间：
2001-04-24
影响因子：
11.1
作者：
Ino, M;Yoshinaga, T;Mori, Y
通讯作者：
Mori, Y
影响因子：
4.8
作者：
Murakami, M;Ohba, T;Iijima, T
通讯作者：
Iijima, T
影响因子：
21.3
作者：
Koulen, P;Cai, YQ;Somlo, S
通讯作者：
Somlo, S