CHARACTERIZATION OF ACID-SENSING ION CHANNELS IN MEDIUM SPINY NEURONS OF MOUSE STRIATUM
CHARACTERIZATION OF ACID-SENSING ION CHANNELS IN MEDIUM SPINY NEURONS OF MOUSE STRIATUM
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DOI：
10.1016/j.neuroscience.2009.04.029
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发表时间：
2009-08-04
期刊：
影响因子：
3.3
通讯作者：
Chu, X. -P.
中科院分区：
文献类型：
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作者：
Jiang, Q.;Li, M. -H.;Chu, X. -P.
酸敏感离子通道 (ASIC) 调节突触活动并在神经退行性疾病中发挥重要作用。它们在纹状体中高度表达，其中中等棘神经元 (MSN) 是主要群体。鉴于 MSN 中 ASIC 的特性尚不清楚，在本研究中，我们对小鼠纹状体 MSN 中的 ASIC 进行了表征。细胞外 pH 值的快速下降会在所有 MSN 中诱导瞬时内向电流。半最大激活的 pH 值为 6.25，接近同聚 ASIC1a 通道中获得的 pH 值。根据 psalmotoxin 1 和锌敏感性，ASIC1a（70.5% 的神经元）和异聚 ASIC1a-2 通道（29.5% 的神经元）似乎与 MSN 中的酸诱导电流有关。 ASIC1 小鼠的 MSN 中 ASIC 电流减少，但 ASIC2 无效小鼠的 MSN 中 ASIC 电流没有减少。此外，pH 值下降可通过激活同聚 ASIC1a 通道诱导钙内流。 ASIC 的激活增加了 MSN 的膜兴奋性并降低了细胞外 Ca2+ 增强的 ASIC 电流。我们的数据表明同聚 ASIC1a 通道代表了 MSN 中大部分 ASIC 同工型。 ASIC 在纹状体中的潜在功能需要进一步研究。由 Elsevier Ltd 代表 IBRO 出版。
Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. They are highly expressed in the striatum, where medium spiny neurons (MSNs) are a major population. Given that the properties of ASICs in MSNs are unknown, in this study, we characterized ASICs in MSNs of the mouse striatum. A rapid drop in extracellular pH induced transient inward currents in all MSNs. The pH value for half-maximal activation was 6.25, close to that obtained in homomeric ASIC1a channels. Based on psalmotoxin 1 and zinc sensitivity, ASIC1a (70.5% of neurons) and heteromeric ASIC1a-2 channels (29.5% of neurons) appeared responsible for the acid-induced currents in MSNs. ASIC currents were diminished in MSNs from ASIC1, but not ASIC2, null mice. Furthermore, a drop in pH induced calcium influx by activating homomeric ASIC1a channels. Activation of ASICs increased the membrane excitability of MSNs and lowering extracellular Ca2+ potentiated ASIC currents. Our data suggest that the homomeric ASIC1a channel represents a majority of the ASIC isoform in MSNs. The potential function of ASICs in the striatum requires further investigation. Published by Elsevier Ltd on behalf of IBRO.