ZD7288抑制低阈值Ca(2+)通道活性并调节精子功能。
ZD7288 inhibits low-threshold Ca(2+) channel activity and regulates sperm function.
作者信息
Felix Ricardo, Sandoval Alejandro, Sánchez Daniel, Gómora Juan Carlos, De la Vega-Beltrán José L, Treviño Claudia L, Darszon Alberto
机构信息
Department of Physiology, Biophysics and Neuroscience, Cinvestav-IPN, Mexico City, Mexico.
出版信息
Biochem Biophys Res Commun. 2003 Nov 7;311(1):187-92. doi: 10.1016/j.bbrc.2003.09.197.
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) Ca(2+) channels have. Interestingly, ZD7288 blocked native T-type Ca(2+) currents in mouse spermatogenic cells with an IC(50) of about 100 microM. 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 Ca(2+) channels in the mouse sperm AR.
在本研究中，已发现超极化激活的环核苷酸门控（HCN）通道阻滞剂ZD7288可抑制小鼠精子顶体反应（AR）。尚未记录到HCN通道与小鼠精子AR有关，但低阈值（T型）Ca(2+)通道与之有关。有趣的是，ZD7288以约100微摩尔的半数抑制浓度（IC(50)）阻断小鼠生精细胞中的天然T型Ca(2+)电流。这种阻断在产生低水平失活的电压下更有效，表明ZD7288对不同通道构象具有不同的亲和力。此外，ZD7288抑制在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Ca(2+)通道在小鼠精子AR中的作用。
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