Kir6.2-deficient mice are susceptible to stimulated ANP secretion:: KATP channel acts as a negative feedback mechanism?
Kir6.2-deficient mice are susceptible to stimulated ANP secretion:: KATP channel acts as a negative feedback mechanism?
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DOI：
10.1016/j.cardiores.2005.03.011
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发表时间：
2005-07-01
影响因子：
10.8
通讯作者：
Nakaya, H
中科院分区：
文献类型：
--
作者：
Saegusa, N;Sato, T;Nakaya, H
目的：虽然心房钠尿肽（ANP）已被证明主要由心肌细胞释放以响应心房扩张，但 ANP 分泌的调节机制仍不完全清楚。我们试图使用 Kir6.2（心脏 K-ATP 通道的成孔亚基）基因纯合敲除小鼠来确定 ATP 敏感的 K+ (K-ATP) 通道是否调节 ANP 的分泌。方法：使用膜片钳技术记录分离的小鼠心房细胞的 K-ATP 通道电流。通过放射免疫测定法测定麻醉小鼠的血浆 ANP 浓度以及离体心房制剂中的 ANP 含量和分泌。记录离体心房的动作电位。 结果：暴露于 2,4-二硝基苯酚 (100 μM) 会在野生型 (WT) 而非 Kir6.2 敲除 (Kir6.2 KO) 小鼠的心房细胞中诱发格列本脲敏感的 K-ATP 通道电流。尽管WT和Kir6.2 KO小鼠之间的基础血浆ANP水平没有显着差异，但扩容导致Kir6.2 KO小鼠血浆ANP浓度显着升高，但伴有低血压的WT小鼠则不然。当分离的左心房被拉伸时，Kir6.2 KO心房分泌到浴中的ANP显着高于WT心房。此外，拉伸 WT 而非 Kir6.2 KO 小鼠的心房显着缩短了动作电位持续时间。膜的低渗拉伸会在 WT 小鼠的心房细胞中诱导格列本脲敏感的 K-ATP 通道电流，但不会在 Kir6.2 KO 小鼠中诱导。结论：Kir6.2 对于小鼠心房细胞中 K-ATP 通道的功能至关重要。鉴于Kir6.2。 KO 小鼠容易受到拉伸诱导的 ANP 分泌的影响，我们的结果表明 K-ATP 通道可能充当控制 ANP 分泌的负反馈机制。 (c) 2005 年欧洲心脏病学会。由 Elsevier B.V. 出版。保留所有权利。
Objective: While atrial natriuretic peptide (ANP) has been shown to be released mainly from cardiac muscle cells in response to atrial distension, the regulatory mechanisms of ANP secretion are still not fully understood. We sought to determine whether the ATP-sensitive K+ (K-ATP) channel modulates the secretion of ANP, using mice with homozygous knockout of the Kir6.2 (a pore-forming subunit of cardiac K-ATP channel) gene.Methods: K-ATP channel currents were recorded from isolated mouse atrial cells with patch-clamp techniques. Plasma ANP concentrations in anesthetized mice and ANP content and secretion in isolated atrial preparations were determined by radio immunoassay. Action potentials were recorded from the isolated atria.Results: Exposure to 2,4-dinitrophenol (100 mu M) evoked a glibenclamide-sensitive K-ATP channel current in atrial cells from wild-type (WT) but not Kir6.2 knockout (Kir6.2 KO) mice. Although there were no significant differences in the basal plasma ANP levels between WT and Kir6.2 KO mice, volume expansion caused a significant elevation of plasma ANP concentration in Kir6.2 KO but not WT mice with accompanying hypotension. When isolated left atria were stretched, ANP secreted into the bath from Kir6.2 KO atria was significantly higher than that from WT atria. Furthermore, stretching the atria from WT but not Kir6.2 KO mice significantly shortened the action potential duration. A hypotonic stretch of the membrane induced the glibenclamide-sensitive K-ATP channel current in atrial cells from WT but not Kir6.2 KO mice.Conclusions: Kir6.2 is essential for the function of K-ATP channel in mouse atrial cells. Given that Kir6.2. KO mice Are susceptible to stretch-induced secretion of ANP, our results suggest that K-ATP channels may act as a negative feedback mechanism for the control of ANP secretion. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.