Electrical Slow Waves in the Mouse Oviduct Are Dependent upon a Calcium Activated Chloride Conductance Encoded by Tmem16a
Electrical Slow Waves in the Mouse Oviduct Are Dependent upon a Calcium Activated Chloride Conductance Encoded by Tmem16a
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DOI：
10.1095/biolreprod.111.095554
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发表时间：
2012-01-01
影响因子：
3.6
通讯作者：
Ward, Sean M.
中科院分区：
文献类型：
--
作者：
Dixon, Rose Ellen;Hennig, Grant W.;Ward, Sean M.
输卵管肌收缩对卵母细胞沿输卵管沿着运输至关重要。一群专门的起搏细胞--输卵管Cajal间质细胞--产生慢波，这是输卵管肌收缩的基础电事件。输卵管起搏点活动的离子基础尚不清楚。我们研究了一类新的Ca 2+激活的Cl-通道（CaCCs）-anoctamin 1（由Tmem 16 a编码）在输卵管慢波产生中的作用。RT-PCR显示Tmem 16 a编码的CaCCs在输卵管肌中有转录表达。在蒽-9-羧酸和尼氟灭酸两种不同的氯离子通道拮抗剂存在下进行细胞内微电极记录。这两种抑制剂引起膜超极化，减少慢波的持续时间，并最终抑制起搏器的活动。硝氟酸也抑制输卵管肌内钙波的传播。在野生型和杂合子输卵管出生时出现慢波，但在Tmem 16 a无效等位基因纯合子小鼠（Tmem 16 a（tm 1Bdh/tm 1Bdh））出生时未能出现慢波。这些数据表明，Tmem 16 a编码的CaCC有助于膜电位，并负责输卵管慢波的上行和平台期。
Myosalpinx contractions are critical for oocyte transport along the oviduct. A specialized population of pacemaker cells-oviduct interstitial cells of Cajal-generate slow waves, the electrical events underlying myosalpinx contractions. The ionic basis of oviduct pacemaker activity is unknown. We examined the role of a new class of Ca2+-activated Cl- channels (CaCCs)-anoctamin 1, encoded by Tmem16a-in oviduct slow wave generation. RT-PCR revealed the transcriptional expression of Tmem16a-encoded CaCCs in the myosalpinx. Intracellular microelectrode recordings were performed in the presence of two pharmacologically distinct Cl- channel antagonists, anthracene-9-carboxylic acid and niflumic acid. Both of these inhibitors caused membrane hyperpolarization, reduced the duration of slow waves, and ultimately inhibited pacemaker activity. Niflumic acid also inhibited propagating calcium waves within the myosalpinx. Slow waves were present at birth in wild-type and heterozygous oviducts but failed to develop by birth in mice homozygous for a null allele of Tmem16a (Tmem16a(tm1Bdh/tm1Bdh)). These data suggest that Tmem16a-encoded CaCCs contribute to membrane potential and are responsible for the upstroke and plateau phases of oviduct slow waves.