DHP‐insensitive L‐type‐like Ca channel of ascidian acquires sensitivity to DHP with single amino acid change in domain III P‐region

TuCa1, an ascidian homolog of L‐type Ca channel α1‐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 Ala1016 at the P‐region of domain III in TuCa1 (TuCa1/A1016S) and functionally expressed the channel in Xenopus oocyte along with rabbit α2/δ and β2b. 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 Ser1016 in TuCa1/A1016S participates in DHP binding, but there exist other novel sites that fully acquire sensitivity to FPL‐64176.