Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels.
Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels.
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在生理离子条件下对人类精子的斑块夹研究揭示了三个在功能和药理上不同的阳离子通道。
DOI：
10.1093/molehr/gau003
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发表时间：
2014-05
影响因子：
4
通讯作者：
Wilson SM
中科院分区：
文献类型：
--
作者：
Mansell SA;Publicover SJ;Barratt CL;Wilson SM
虽然精子的电容量取决于允许精子膜电位（Vm）保持在负值的K+电导（GK），但人类精子中这种电导的特征实际上是未知的。因此，我们研究了生物物理/药理学特性的K+电导在精子从正常的捐助者下举行的电压/电流钳在全细胞记录配置。我们的标准记录条件旨在保持准生理性的Na+、K+和Cl−梯度。探索离子取代/离子通道阻断剂对膜电流/电位的影响的实验表明，静息Vm依赖于通过仅显示弱电压依赖性和有限（约7倍）K+对Na+选择性的通道流动的超极化K+电流。奎尼丁（0.3 mM）、布比卡因（3 mM）和氯非铵（50 µM）、NNC 55 -0396（2 µM）和米贝拉地尔（30 µM）可阻断该电导，但4-氨基吡啶（2 mM，4-AP）不能阻断该电导。孕酮对超极化钾电流无影响。测试去极化后的复极化一致地诱发了瞬时向内的“尾电流”（ITail），该尾电流通过具有差的（约3倍）K+对Na+选择性的第二个离子通道群体流动。奎尼丁、4-AP和孕酮可增加这些通道的活性。因此，人类精子中的Vm依赖于超极化K+电流，该电流通过与Slo 3编码的通道最相似的通道流动。虽然0.5 μM孕酮对这些通道没有影响，但这种激素确实激活了介导ITail的两个不同的通道。总之，本研究揭示了三个功能和结构不同的阳离子通道：Ik，ITail，ICatSper。
Whilst fertilizing capacity depends upon a K+ conductance (GK) that allows the spermatozoon membrane potential (Vm) to be held at a negative value, the characteristics of this conductance in human sperm are virtually unknown. We therefore studied the biophysical/pharmacological properties of the K+ conductance in spermatozoa from normal donors held under voltage/current clamp in the whole cell recording configuration. Our standard recording conditions were designed to maintain quasi-physiological, Na+, K+ and Cl− gradients. Experiments that explored the effects of ionic substitution/ion channel blockers upon membrane current/potential showed that resting Vm was dependent upon a hyperpolarizing K+ current that flowed via channels that displayed only weak voltage dependence and limited (∼7-fold) K+ versus Na+ selectivity. This conductance was blocked by quinidine (0.3 mM), bupivacaine (3 mM) and clofilium (50 µM), NNC55-0396 (2 µM) and mibefradil (30 µM), but not by 4-aminopyridine (2 mM, 4-AP). Progesterone had no effect upon the hyperpolarizing K+ current. Repolarization after a test depolarization consistently evoked a transient inward ‘tail current’ (ITail) that flowed via a second population of ion channels with poor (∼3-fold) K+ versus Na+ selectivity. The activity of these channels was increased by quinidine, 4-AP and progesterone. Vm in human sperm is therefore dependent upon a hyperpolarizing K+ current that flows via channels that most closely resemble those encoded by Slo3. Although 0.5 µM progesterone had no effect upon these channels, this hormone did activate the pharmacologically distinct channels that mediate ITail. In conclusion, this study reveals three functionally and pharmacologically distinct cation channels: Ik, ITail, ICatSper.
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影响因子：
6.7
作者：
Fabbri, R;Porcu, E;Flamigni, C
通讯作者：
Flamigni, C
影响因子：
4.8
作者：
Hernandez-Gonzalez, Enrique O.;Trevino, Claudia L.;Darszon, Alberto
通讯作者：
Darszon, Alberto
影响因子：
2.7
作者：
Acevedo, JJ;Mendoza-Lujambio, I;Darszon, A
通讯作者：
Darszon, A
DOI：
10.1073/pnas.1215078109
发表时间：
2012-11-20
影响因子：
11.1
作者：
Leonetti, Manuel D.;Yuan, Peng;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
1.7
作者：
Felix, R;Serrano, CJ;Darszon, A
通讯作者：
Darszon, A