Signal transduction mechanism of cardiac stretch-activated channels

The cardiac myocytes总是在物理力量的影响下，与ion channels regulated by stretch may play important physiological roles in the heart. This研究项目，thereforewas designed to clarify the signal transduction mechanism around the stretch-activated ion channelsin the molecular level. Candidate molecules interacting with several stretch-activated chloridechannels were screened from cardiac cDNA library using the yeast two-hybrid method. the carboxylClC-2通道的终端被发现与三个模块之间的互动，这是规范的使用thecell cycle. In vitro kinase assay revealed that the carboxyl terminus of ClC-2 wasphosphorylated by p34 D1cdc2 D1/cycin B and MAP kinase. ClC-2 currents expressed in Xenopusoocytes were inhibited by p34 D1cdc2 D1/cyclin B, and were augmented by olomoucine，a cyclin-dependent kinase inhibitor. The reverse transcription PCR技术演示that The mRNAClC-2 level of cell cycle这些数据应该是ClC-2通道was，这是规范在fetal and hypertrophied heartcell cycle machinery in the level of transcription, protein phosphorylation这些方法可能被important to achieve drastic change of cell volumeduring the course of cell cycle。

The cardiac myocytes are always under the influence of physical force, and ion channels regulated by stretch may play important physiological roles in the heart. This research project, therefore, was designed to clarify the signal transduction mechanism around the stretch-activated ion channels in the molecular level. Candidate molecules interacting with several stretch-activated chloride channels were screened from cardiac cDNA library using the yeast two-hybrid method. The carboxyl terminus of ClC-2 channel was found to interact with three molecules that are regulated during the course of cell cycle. In vitro kinase assay revealed that the carboxyl terminus of ClC-2 was phosphorylated by p34ィイD1cdc2ィエD1/cycin B and MAP kinase. ClC-2 currents expressed in Xenopus oocytes were inhibited by p34ィイD1cdc2ィエD1/cyclin B, and were augmented by olomoucine, a cyclin-dependent kinase inhibitor. The reverse transcription PCR technique showed that the mRNA level of ClC-2 was also regulated by cell cycle, and was up-regulated in the fetal and hypertrophied heart. These data showed that ClC-2 channel was regulated by cell cycle machinery in the level of transcription, protein phosphorylation, and channel function. These mechanism may be important to achieve drastic change of cell volume during the course of cell cycle.