Mechanosensitive ion channel Piezo2 is inhibited by D-GsMTx4
Mechanosensitive ion channel Piezo2 is inhibited by D-GsMTx4
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DOI：
10.1080/19336950.2017.1279370
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发表时间：
2017-01-01
期刊：
影响因子：
3.3
通讯作者：
Beyder, Arthur
中科院分区：
文献类型：
--
作者：
Alcaino, Constanza;Knutson, Kaitlyn;Beyder, Arthur
肠嗜铬 ((EC)) 细胞是胃肠道 (GI) 上皮的主要机械传感器。为了响应机械刺激 (EC)，细胞释放血清素（5-羟色胺；5-HT）。 (EC) 细胞机械敏感性的分子细节知之甚少。最近，我们课题组发现人和小鼠（EC）细胞表达机械敏感离子通道Piezo2。人（EC）细胞模型 QGP-1 中的机械敏感电流被机械敏感通道阻断剂 D-GsMTx4 阻断。在本研究中，我们旨在表征机械敏感离子通道抑制剂蜘蛛肽 D-GsMTx4 对 QGP-1 和人 Piezo2 转染 HEK-293 细胞的机械刺激电流的影响。我们通过免疫组织化学发现 5-HT 和 Piezo2 在 QGP-1 细胞中共定位。 QGP-1 机械敏感电流具有与剂量依赖性 Piezo2 相似的生物物理特性，并被 D-GsMTx4 抑制。为了响应细胞膜的直接位移，在 HEK-293 细胞中瞬时表达的人 Piezo2 产生强大的快速激活和失活内向电流。 D-GsMTx4 可逆且剂量依赖性地抑制 Piezo2 电流响应机械力的效力和功效。我们的数据证明蜘蛛肽 D-GsMTx4 可有效抑制 Piezo2 机械敏感电流。
Enterochromaffin ((EC)) cells are the primary mechanosensors of the gastrointestinal (GI) epithelium. In response to mechanical stimuli(EC) cells release serotonin (5-hydroxytryptamine; 5-HT). The molecular details of(EC) cell mechanosensitivity are poorly understood. Recently, our group found that human and mouse(EC) cells express the mechanosensitive ion channel Piezo2. The mechanosensitive currents in a human(EC) cell model QGP-1 were blocked by the mechanosensitive channel blocker D-GsMTx4.In the present study we aimed to characterize the effects of the mechanosensitive ion channel inhibitor spider peptide D-GsMTx4 on the mechanically stimulated currents from both QGP-1 and human Piezo2 transfected HEK-293 cells. We found co-localization of 5-HT and Piezo2 in QGP-1 cells by immunohistochemistry. QGP-1 mechanosensitive currents had biophysical properties similar to dose-dependently Piezo2 and were inhibited by D-GsMTx4. In response to direct displacement of cell membranes, human Piezo2 transiently expressed in HEK-293 cells produced robust rapidly activating and inactivating inward currents. D-GsMTx4 reversibly and dose-dependently inhibited both the potency and efficacy of Piezo2 currents in response to mechanical force. Our data demonstrate an effective inhibition of Piezo2 mechanosensitive currents by the spider peptide D-GsMTx4.