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DHP‐insensitive L‐type‐like Ca channel of ascidian acquires sensitivity to DHP with single amino acid change in domain III P‐region
Author(s) -
Izumi-Nakaseko Hiroko,
Yamaguchi Shinji,
Ohtsuka Yukio,
Ebihara Tatsuhiko,
Adachi-Akahane Satomi,
Okamura Yasushi
Publication year - 2003
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(03)00772-5
Subject(s) - xenopus , protein subunit , chemistry , stereochemistry , alpha (finance) , oocyte , biophysics , biology , microbiology and biotechnology , biochemistry , gene , medicine , embryo , construct validity , nursing , patient satisfaction
TuCa1, an ascidian homolog of L‐type Ca channel α 1 ‐subunit, has many critical sites required for binding 1,4‐dihydropyridines (DHPs), but is insensitive to DHPs and methyl 2,5‐dimethyl‐4‐[2‐(phenylmethyl)benzoyl]‐1H‐pyrrole‐3‐carboxylate (FPL‐64176). We have substituted Ser for Ala 1016 at the P‐region of domain III in TuCa1 (TuCa1/A1016S) and functionally expressed the channel in Xenopus oocyte along with rabbit α 2 /δ and β 2b . TuCa1/A1016S has gained DHP sensitivity as high as that of a mammalian neuronal L‐type Ca channel (rbCII), but remained resistant to FPL‐64176. These results reinforce the view that Ser 1016 in TuCa1/A1016S participates in DHP binding, but there exist other novel sites that fully acquire sensitivity to FPL‐64176.