Alteration in ion channel function of mouse nicotinic acetylcholine receptor by mutations in the M4 transmembrane domain.
Alteration in ion channel function of mouse nicotinic acetylcholine receptor by mutations in the M4 transmembrane domain.
复制标题
M4 跨膜结构域突变改变小鼠烟碱乙酰胆碱受体的离子通道功能。
DOI：
10.1007/s002329900545
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Lasalde-Dominicci,JA
中科院分区：
文献类型：
--
作者：
Tamamizu,S;Lee,Y;Hung,B;McNamee,MG;Lasalde-Dominicci,JA
The effect of structural alterations of the M4 transmembrane segment in theTorpedo californicaAChR has shown that substitution of specific residues can be critical to the channel gating (Lasalde et al., 1996). In a previous study we found that phenylalanine and tryptophan substitutions at the αC418 residue in the M4 transmembrane segment of theTorpedo californicaAChR significantly altered ion channel function (Lee et al., 1994; Ortiz-Miranda et al., 1997). Cassette mutagenesis was used to mutate the Cys residue at the corresponding C418 position in the α subunit of mouse AChR. A total of nine mutations on the mouse αC418 position were tested, including the αC418A, αC418V, αC418L, αC418S, αC418M, αC418W, αC418H, αC418E and αC418G mutants. All the mutants tested were functional except the αC418G which was not expressed on the surface of the oocyte. The data obtained from macroscopic and single channel currents demonstrate that different types of amino acids can be accommodated at this presumably lipid-exposed position without loss of ion-channel function. As with theTorpedoAChR, the mutation of Cys to Trp dramatically decreased the EC50for acetylcholine and increased channel open time. The lack of expression of the mouse αC418G suggest that there are some differences in folding, oligomerization and perhaps transport to the surface membrane for this mutant between theTorpedoand the mammalian AChR.
