ZD7288 inhibits low-threshold Ca2+ channel activity and regulates sperm function
ZD7288 inhibits low-threshold Ca2+ channel activity and regulates sperm function
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DOI：
10.1016/j.bbrc.2003.09.197
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发表时间：
2003-11-07
影响因子：
3.1
通讯作者：
Darszon, A
中科院分区：
文献类型：
--
作者：
Felix, R;Sandoval, A;Darszon, A
在这项研究中，发现超极化激活和环核苷酸门控（HCN）通道阻断剂ZD 7288可抑制小鼠精子顶体反应（AR）。HCN通道尚未被记录或涉及小鼠精子AR，但低阈值（T型）Ca 2+通道。有趣的是，ZD 7288阻断小鼠生精细胞中的天然T型Ca 2+电流，IC 50约为100 μ M。这种阻断在产生低水平失活的电压下更有效，表明ZD 7288对不同通道构象的亲和力不同。此外，ZD 7288抑制HEK-293细胞中异源表达的所有克隆T型通道，但不抑制高阈值N型通道。我们的结果进一步支持了T型钙通道在小鼠精子AR中的作用。(C)2003年爱思唯尔公司All rights reserved.
in this study, ZD7288, a blocker of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, has been found to inhibit the mouse sperm acrosome reaction (AR). HCN channels have not yet been either recorded or implicated in mouse sperm AR, but low-threshold (T-type) Ca2+ channels have. Interestingly, ZD7288 blocked native T-type Ca2+ currents in mouse spermatogenic cells with an IC50 of about 100 muM. This blockade was more effective at voltages producing low levels of inactivation, suggesting a differential affinity of ZD7288 for different channel conformations. Furthermore, ZD7288 inhibited all cloned T-type but not high-threshold N-type channels heterologously expressed in HEK-293 cells. Our results further support the role of T-type Ca2+ channels in the mouse sperm AR. (C) 2003 Elsevier Inc. All rights reserved.