Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents.
Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents.
复制标题
DOI：
10.1113/jphysiol.2009.170159
复制
发表时间：
2009-05-15
期刊：
影响因子：
--
通讯作者：
Main M
中科院分区：
文献类型：
--
作者：
Hamann M;Gibson A;Davies N;Jowett A;Walhin JP;Partington L;Affleck K;Trezise D;Main M
包括人类ClCa1 （hClCa1）在内的CLCA基因家族蛋白被认为构成了一个新的氯离子通道家族，介导Ca2+依赖的Cl -电流。本研究利用hClCa1在HEK293和NCIH522细胞系中的异源表达和全细胞记录，研究了hClCa1蛋白与Ca2+依赖性Cl -电流之间的关系。与先前报道的HEK293细胞中不存在Cl -电流相反，我们发现HEK293和NCIH522细胞系表达组成型Ca2+依赖性Cl -电流，并表明hClCa1增加了这些细胞中Ca2+依赖性Cl -电流的振幅。我们进一步表明，hClCa1不改变渗透率序列，但增加了Cl -电导，同时将GSCN - /GCl -电导比从~ 2-3降低到~ 1。我们使用了一个环速率理论（两个能垒，一个位垒）模型，并表明hClCa1对阴离子通道的影响可以通过降低第一和第二能垒的作用来模拟。我们得出结论，hClCa1本身不会形成Ca2+依赖的Cl -通道，也不会增强HEK293和NCIH522表达系统中组成通道的运输/插入。相反，hClCa1通过降低离子通过孔转运的能量屏障，提高内源性Ca2+依赖的Cl -通道的单通道电导。
Proteins of the CLCA gene family including the human ClCa1 (hClCa1) have been suggested to constitute a new family of chloride channels mediating Ca2+-dependent Cl− currents. The present study examines the relationship between the hClCa1 protein and Ca2+-dependent Cl− currents using heterologous expression of hClCa1 in HEK293 and NCIH522 cell lines and whole cell recordings. By contrast to previous reports claiming the absence of Cl− currents in HEK293 cells, we find that HEK293 and NCIH522 cell lines express constitutive Ca2+-dependent Cl− currents and show that hClCa1 increases the amplitude of Ca2+-dependent Cl− currents in those cells. We further show that hClCa1 does not modify the permeability sequence but increases the Cl− conductance while decreasing the GSCN−/GCl− conductance ratio from ∼2–3 to ∼1. We use an Eyring rate theory (two barriers, one site channel) model and show that the effect of hClCa1 on the anionic channel can be simulated by its action on lowering the first and the second energy barriers. We conclude that hClCa1 does not form Ca2+-dependent Cl− channels per se or enhance the trafficking/insertion of constitutive channels in the HEK293 and NCIH522 expression systems. Rather, hClCa1 elevates the single channel conductance of endogenous Ca2+-dependent Cl− channels by lowering the energy barriers for ion translocation through the pore.
登录
查看更多内容
DOI：
10.1164/ajrccm.165.8.2107068
发表时间：
2002-04-15
影响因子：
24.7
作者：
Hoshino, M;Morita, S;Fujino, M
通讯作者：
Fujino, M
影响因子：
3.4
作者：
Corry, B
通讯作者：
Corry, B
影响因子：
4.5
作者：
Green-McKenzie, Judith;Shofer, Frances S.
通讯作者：
Shofer, Frances S.
影响因子：
5.5
作者：
Loewen, ME;Smith, NK;Forsyth, GW
通讯作者：
Forsyth, GW
影响因子：
56.9
作者：
Caputo, Antonella;Caci, Emanuela;Galietta, Luis J. V.
通讯作者：
Galietta, Luis J. V.