Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle, and vascular K-ATP channels
Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle, and vascular K-ATP channels
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DOI：
10.2337/diabetes.45.10.1439
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发表时间：
1996-10-01
期刊：
影响因子：
7.7
通讯作者：
Burant, CF
中科院分区：
文献类型：
--
作者：
Chutkow, WA;Simon, MC;Burant, CF
ATP 敏感的内向整流钾通道在多种组织中表达，包括心脏、骨骼、平滑肌以及胰腺 beta-cens。生理学和药理学研究表明这些组织中存在不同的 K-ATP 通道。最近，通过磺酰脲结合蛋白 SUR 和内向整流 K+ 通道亚基 K1R6.2 的共表达，β-cens 的 K-ATP 通道已以功能形式重建。在本文中，我们描述了从小鼠 SUR2A 和 SUR2B 中分离编码 SUR 样蛋白的 cDNA。 Northern 印迹显示，SURE 亚型的表达最高的是心脏和骨骼肌，而在所有其他组织中表达量较低。通过逆转录聚合酶链式反应，SUR2B 普遍表达，而明显可变剪接的变体 SUR2A 仅在心脏中表达。原位杂交显示，SUR2亚型在心脏和骨骼肌的实质以及其他组织的血管结构中表达。通过荧光原位杂交将人 SURE 定位于 12 号染色体 p12.1。预测蛋白的结构和SUR2的表达模式表明它是胰外K-ATP通道的药物结合通道调节亚基。 SUR 和 SUR2 亚型之间的序列差异可能是 K-ATP 通道组织特异性药理学的基础。
ATP-sensitive inwardly rectifying potassium channels are expressed in a variety of tissues, including heart, skeletal, and smooth muscle, and pancreatic beta-cens. Physiological and pharmacological studies suggest the presence of distinct K-ATP channels in these tissues. Recently, the K-ATP channel of beta-cens has been reconstituted in functional form by coexpression of SUR, the sulfonylurea-binding protein, and the inwardly rectifying K+ channel subunit, K1R6.2. In this article, we describe the isolation of cDNAs encoding SUR-like proteins from mouse, SUR2A and SUR2B. Northern blotting showed that the highest expression of the SURE isoforms is in the heart and skeletal muscle, with lower levels in all other tissues. By reverse transcription-polymerase chain reaction, SUR2B is ubiquitously expressed, while the apparently alternatively spliced variant, SUR2A, is expressed exclusively in heart. In situ hybridization shows that the SUR2 isoforms are expressed in the parenchyma of the heart and skeletal muscle and in the vascular structures of other tissues. Human SURE was localized to chromosome 12, p12.1 by fluorescent in situ hybridization. The structure of the predicted protein and expression pattern of SUR2 suggests that it is the drug-binding channel-modulating subunit of the extrapancreatic K-ATP channel. Differences in sequence between SUR and between SUR2 isoforms may underlie the tissue-specific pharmacology of the K-ATP channel.