Voltage-dependent modulation of T-type calcium channels by protein tyrosine phosphorylation
Voltage-dependent modulation of T-type calcium channels by protein tyrosine phosphorylation
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DOI：
10.1093/emboj/16.7.1593
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发表时间：
1997-04-01
期刊：
影响因子：
11.4
通讯作者：
Florman, HM
中科院分区：
文献类型：
--
作者：
Arnoult, C;Lemos, JR;Florman, HM
T型Ca2+通道在小鼠雄性生殖谱系分化期间表达，并保留在精子中，在精子中通过与卵子的细胞外基质接触而被激活，并控制精子顶体胞吐。在这里，我们研究了这种钙离子通道的调节在分离的小鼠生精细胞使用全细胞膜片钳技术，T电流增强，或促进，强去极化或高频刺激后。电压依赖性的促进增加了Ca2+电流的平均50%。蛋白酪氨酸激酶活性的拮抗剂也产生同样的促进作用。相反，酪氨酸磷酸酶活性的拮抗剂阻断电流的电压依赖性促进作用。这些数据与两态模型的存在一致，其中T通道通过紧张性酪氨酸磷酸化维持在低（或零）电导状态，并且可以通过酪氨酸磷酸酶活性激活到高电导状态，酪氨酸磷酸化状态对该通道的正性和负性调节为哺乳动物早期精子活动的控制提供了可能的机制。受精
A T-type Ca2+ channel is expressed during differentiation of the male germ lineage in the mouse and is retained in sperm, where is it activated by contact with the the egg's extracellular matrix and controls sperm acrosomal exocytosis. Here, we examine the regulation of this Ca2+ channel in dissociated spermatogenic cells from the mouse using the whole-cell patch-clamp technique, T currents were enhanced, or facilitated, after strong depolarizations or high frequency stimulation. Voltage-dependent facilitation increased the Ca2+ current by an average of 50%. The same facilitation is produced by antagonists of protein tyrosine kinase activity, Conversely, antagonists of tyrosine phosphatase activity block voltage-dependent facilitation of the current. These data are consistent with the presence of a two-state model, in which T channels are maintained in a low (or zero) conductance state by tonic tyrosine phosphorylation and can be activated to a high conductance state by a tyrosine phosphatase activity, The positive and negative modulation of this channel by the tyrosine phosphorylation state provides a plausible mechanism for the control of sperm activity during the early stages of mammalian fertilization.