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Coexpression of a Ca v 1.2 protein lacking an N‐terminus and the first domain specifically suppresses L‐type calcium channel activity
Author(s) -
Ebihara Tatsuhiko,
Komiya Yuriko,
Izumi-Nakaseko Hiroko,
Adachi-Akahane Satomi,
Okabe Shigeo,
Okamura Yasushi
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03340-9
Subject(s) - xenopus , protein subunit , n type calcium channel , voltage dependent calcium channel , wild type , calcium channel , western blot , mutant , r type calcium channel , microbiology and biotechnology , biology , hek 293 cells , calcium , l type calcium channel , oocyte , t type calcium channel , chemistry , biochemistry , gene , embryo , organic chemistry
L‐type Ca 2 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 v 1.2 was designed by mimicking an ascidian 3‐domain‐type α1 subunit (that inhibits the full‐length subunit's current). The 3‐domain‐type Ca v 1.2 subunit significantly inhibited wild‐type Ca v 1.2 current, but not other ionic currents such as Ca v 2.1 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.