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Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons.

机译:通过海马神经元中共定位的Ca2 +通道选择性激活Ca2 +激活的K +通道。

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Calcium entry through voltage-gated calcium channels can activate either large- (BK) or small- (SK) conductance calcium-activated potassium channels. In hippocampal neurons, activation of BK channels underlies the falling phase of an action potential and generation of the fast afterhyperpolarization (AHP). In contrast, SK channel activation underlies generation of the slow AHP after a burst of action potentials. The source of calcium for BK channel activation is unknown, but the slow AHP is blocked by dihydropyridine antagonists, indicating that L-type calcium channels provide the calcium for activation of SK channels. It is not understood how this specialized coupling between calcium and potassium channels is achieved. Here we study channel activity in cell-attached patches from hippocampal neurons and report a unique specificity of coupling. L-type channels activate SK channels only, without activating BK channels present in the same patch. The delay between the opening of L-type channels and SK channels indicates that these channels are 50-150 nm apart. In contrast, N-type calcium channels activate BK channels only, with opening of the two channel types being nearly coincident. This temporal association indicates that N and BK channels are very close. Finally, P/Q-type calcium channels do not couple to either SK or BK channels. These data indicate an absolute segregation of coupling between channels, and illustrate the functional importance of submembrane calcium microdomains.
机译:钙通过电压门控钙通道的进入可以激活大(BK)或小(SK)电导的钙激活钾通道。在海马神经元中,BK通道的激活是动作电位下降阶段和快速超极化后(AHP)产生的基础。相反,在动作电位爆发后,SK通道激活是缓慢AHP产生的基础。用于BK通道激活的钙的来源尚不清楚,但是缓慢的AHP被二氢吡啶拮抗剂阻断,表明L型钙通道为激活SK通道提供了钙。还不知道如何实现钙和钾通道之间的这种专门偶联。在这里,我们研究海马神经元的细胞贴片中的通道活性,并报道了偶联的独特特异性。 L型通道仅激活SK通道,而不激活同一补丁中存在的BK通道。 L型通道和SK通道打开之间的延迟表明这些通道之间相距50-150 nm。相反,N型钙通道仅激活BK通道,两种通道类型的打开几乎重合。这种时间上的关联表明N和BK通道非常接近。最后,P / Q型钙通道不与SK或BK通道耦合。这些数据表明通道之间耦合的绝对隔离,并说明了膜下钙微结构域的功能重要性。

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