Coexpression of a Cav1.2 protein lacking an N‐terminus and the first domain specifically suppresses L‐type calcium channel activity

FEBS Letters

Adachi-Akahane, Satomi¹  Ebihara, Tatsuhiko²  Okabe, Shigeo²  Izumi-Nakaseko, Hiroko²  Okamura, Yasushi²  Komiya, Yuriko¹ 

[1] Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan;Molecular Neurophysiology Group, Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan

关键词: Calcium channel;    L-type;    Truncation;    Specific inhibition;    Xenopus oocyte;   

DOI  :  10.1016/S0014-5793(02)03340-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

L-type Ca² channels play a critical role in many types of cells, including nerve, muscle and endocrine cells. The most popular and effective tools for analyzing the roles of L-type calcium channels (L-channels) are specific antagonists such as dihydropyrigines. With these drugs however, it is difficult to target specific cells. One solution is to develop a genetically targetable inhibitor coded by DNA. As a candidate for such an inhibitor, a dominant negative mutant of Ca_v1.2 was designed by mimicking an ascidian 3-domain-type α1 subunit (that inhibits the full-length subunit's current). The 3-domain-type Ca_v1.2 subunit significantly inhibited wild-type Ca_v1.2 current, but not other ionic currents such as Ca_v2.1 and Na_v channels in Xenopus oocyte expression systems. Western blot analysis showed that the expression of the wild-type protein into the plasma membrane was significantly suppressed on coexpression with the truncated protein. These findings support that an N-terminus-truncated mutant could serve as a specific genetically encoded inhibitor for L-channels.

【 授权许可】

Unknown