Characterization of acid-sensing ion channel expression in oligodendrocyte-lineage cells.
Characterization of acid-sensing ion channel expression in oligodendrocyte-lineage cells.
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DOI：
10.1002/glia.20693
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发表时间：
2008-08-15
期刊：
影响因子：
6.2
通讯作者：
Pleasure, David
中科院分区：
文献类型：
--
作者：
Feldman, Daniel H.;Horiuchi, Makoto;Keachie, Krista;Mccauley, Erica;Bannerman, Peter;Itoh, Aki;Itoh, Takayum;Pleasure, David
酸敏感离子通道(ASIC)广泛表达于神经元，它们服务于疼痛和机械感觉，并有助于学习和记忆。六种ASIC亚单位蛋白形成具有不同生理特性的同或异构体通道复合体。在这些复合体中，只有单体ASIC1a通道是钙离子通透性的。先前的药理学和遗传学研究表明，ASIC1a通道失活显著降低了中枢神经系统对缺血性损伤的敏感性。在这里，我们通过分子、电生理、钙成像和免疫荧光技术来表征ASIC在少突胶质细胞系细胞(OLC)中的表达。ASIC1a、ASIC2a和ASIC4mRNAs在培养的大鼠OLC中表达，这些mRNAs的稳态水平在少突胶质前体细胞中比在成熟少突胶质细胞中高出数倍。在脑白质也检测到ASIC转录本，在白质少突胶质细胞中检测到ASIC1a蛋白表达。全细胞电压钳检测失活、质子门控、阿米洛利敏感的OLC电流。这些电流表现出严重的快速反应和缓慢的恢复，并主要被沙门氏菌毒素阻断，表明在培养的OLC中，同源ASIC1a构成了功能ASIC的很大部分。在电流钳研究中，ASIC的激活显著地使OLC质膜去极化，而在成像研究中，ASIC激活则引起细胞内钙离子的瞬时升高。因此，OLC ASIC1a通道提供了一种途径，通过降低质膜电位和增加钙离子通透性，使中枢神经系统细胞外pH发生酸化，从而激活OLC信号通路，并可能导致OLC对中枢神经系统缺血的易感性。
Acid-sensing ion channels (ASICs) are widely expressed in neurons, where they serve in pain and mechanical sensation, and contribute to learning and memory. Six ASIC subunit proteins form homo- or heteromeric channel complexes with distinct physiological properties. Of such complexes, only monomeric ASIC1a channels are Ca2+ permeable. Prior pharmacologic and genetic studies have shown that ASIC1a channel inactivation markedly diminishes CNS susceptibility to ischemic damage. Here, we characterize ASIC expression in oligodendrocyte lineage cells (OLC) by molecular, electrophysiological, calcium imaging, and immunofluorescence techniques. ASIC1a, ASIC2a, and ASIC4 mRNAs were expressed in cultured rat OLC, with steady-state levels of each of these mRNAs several-fold higher in oligodendroglial progenitors than in mature oligodendroglia. ASIC transcripts were also detected in brain white matter, and ASIC1a protein expression was detected in white matter oligodendroglia. Inactivating, proton-gated, amiloride-sensitive OLC currents were detected by whole-cell voltage clamp. These currents showed profound tachyphylaxis with slow recovery, and were predominantly blocked by psalmotoxin, indicating that homomeric ASIC1a comprised a large fraction of functional ASIC in the cultured OLC. ASIC activation substantially depolarized OLC plasma membrane in current clamp studies, and elicited transient elevations in intracellular Ca2+ in imaging studies. Thus, OLC ASIC1a channels provide a means by which an acid shift in CNS extracellular pH, by diminishing plasma membrane potential and increasing Ca2+ permeability, can activate OLC signaling pathways, and may contribute to OLC vulnerability to CNS ischemia.
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DOI：
10.1085/jgp.200308973
发表时间：
2004-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Paukert M;Babini E;Pusch M;Gründer S
通讯作者：
Gründer S
影响因子：
3.4
作者：
Blankenfeld, Gabriela V.;Verkhratsky, Alexej N.;Kettenmann, Helmut
通讯作者：
Kettenmann, Helmut
影响因子：
6.2
作者：
KIRISCHUK, S;SCHERER, J;KETTENMANN, H
通讯作者：
KETTENMANN, H
影响因子：
3.3
作者：
BORGES, K;OHLEMEYER, C;KETTENMANN, H
通讯作者：
KETTENMANN, H
影响因子：
4.7
作者：
Itoh, T;Beesley, J;Pleasure, D
通讯作者：
Pleasure, D