Activation of mouse sperm T-type Ca2+ channels by adhesion to the egg zona pellucida

Activation of mouse sperm T-type Ca2+ channels by adhesion to the egg zona pellucida
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DOI:
10.1073/pnas.93.23.13004
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发表时间:
1996-11-12
影响因子:
11.1
通讯作者:
Florman, HM
Florman, HM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Arnoult, C;Cardullo, RA;Florman, HM

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精子顶体反应是一种依赖于钙离子的胞吐事件,由粘附到哺乳动物卵子的透明质膜上触发。以前的研究使用离子选择性荧光探针建议的作用,电压敏感的钙离子通道在顶体反应。本文采用全细胞膜片钳技术研究了小鼠精子发生过程中功能性T型钙通道的表达。T型钙通道拮抗剂可抑制生殖细胞T电流(pimozide和amiloride)以及主要作用部位为体细胞L-型Ca 2+通道的拮抗剂(1,4-二氢吡啶,芳基烷基胺,苯并噻唑),如某些体细胞T电流也已报道。在精子中,在配子相互作用过程中抑制T通道抑制透明质酸依赖的Ca 2+升高,如离子选择性荧光探针所示,也抑制顶体反应。这些研究直接将精子T型Ca 2+通道与受精联系起来。此外,1,4-二氢吡啶类对通道抑制的动力学表明了这些化合物在人类男性中报告的避孕作用的机制。
The sperm acrosome reaction is a Ca2+-dependent exocytotic event that is triggered by adhesion to the mammalian egg's zona pellucida. Previous studies using ion-selective fluorescent probes suggested a role of voltage-sensitive Ca2+ channels in acrosome reactions. Here, whole-cell patch clamp techniques are used to demonstrate the expression of functional T-type Ca2+ channels during mouse spermatogenesis, The germ cell T current is inhibited hy antagonists of T-type channels (pimozide and amiloride) as well as by antagonists whose major site of action is the somatic cell L-type Ca2+ channel (1,4-dihydropyridines, arylalkylamines, benzothiazapines), as has also been reported for certain somatic cell T currents. In sperm, inhibition of T channels during gamete interaction inhibits zona pellucida-dependent Ca2+ elevations, as demonstrated by ion-selective fluorescent probes, and also inhibits acrosome reactions. These studies directly link sperm T-type Ca2+ channels to fertilization, In addition, the kinetics of channel inhibition by 1,4-dihydropyridines suggests a mechanism for the reported contraceptive effects of those compounds in human males.