Calcium-activated chloride channels anoctamin 1 and 2 promote murine uterine smooth muscle contractility.

Calcium-activated chloride channels anoctamin 1 and 2 promote murine uterine smooth muscle contractility.
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DOI:
10.1016/j.ajog.2014.06.018
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发表时间:
2014-12
影响因子:
9.8
通讯作者:
Gallos, George
Gallos, George
中科院分区:
医学1区
文献类型:
--
作者:
Bernstein, Kyra;Vink, Joy Y.;Fu, Xiao Wen;Wakita, Hiromi;Danielsson, Jennifer;Wapner, Ronald;Gallos, George

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确定人和小鼠子宫平滑肌中钙激活氯离子通道 anoctamin 1 和 2 的存在,并评估这些离子通道在小鼠子宫肌层收缩力中的生理作用。我们进行了逆转录聚合酶链反应以确定 anoctamin 1 和 2 是否在人类和小鼠子宫组织中表达,以验证该蛋白质在小鼠模型中的研究。然后对 anoctamin 1 和 2 进行免疫组织化学染色以确定小鼠子宫肌层组织中的蛋白质表达。使用电生理学研究、器官浴和钙流实验评估 anoctamin 1 和 2 在小鼠子宫组织中的功能。 Anoctamin 1 和 2 在人和鼠 USM 细胞中表达。功能研究表明,这些通道的选择性拮抗作用可促进小鼠子宫平滑肌自发收缩的松弛。阻断 anoctamin 1 和 2 可抑制激动剂诱导的和自发的瞬时内向电流,并消除 G 蛋白偶联受体(催产素)介导的细胞内钙升高。钙激活的氯离子通道 ANO 1 和 2 存在于人类和小鼠子宫肌层组织中,可能为实现有效安胎提供新的潜在治疗靶点。
To determine the presence of calcium activated chloride channels anoctamin 1 and 2 in human and murine uterine smooth muscle and evaluate the physiologic role for these ion channels in murine myometrial contractility. We performed reverse transcription polymerase chain reaction to determine if anoctamin 1 and 2 are expressed in human and murine uterine tissue to validate the study of this protein in mouse models. Immunohistochemical staining of anoctamin 1 and 2 was then performed to determine protein expression in murine myometrial tissue. The function of anoctamin 1 and 2 in murine uterine tissue was evaluated using electrophysiological studies, organ bath, and calcium flux experiments. Anoctamin 1 and 2 are expressed in human and murine USM cells. Functional studies show that selective antagonism of these channels promotes relaxation of spontaneous murine uterine smooth muscle contractions. Blockade of anoctamin 1 and 2 inhibits both agonist-induced and spontaneous transient inward currents and abolishes G-protein coupled receptor (oxytocin) mediated elevations in intracellular calcium. The calcium activated chloride channels ANO 1 and 2 are present in human and murine myometrial tissue and may provide novel potential therapeutic targets to achieve effective tocolysis.
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