Genetic and pharmacological identification of ion channels central to the Drosophila cardiac pacemaker
Genetic and pharmacological identification of ion channels central to the Drosophila cardiac pacemaker
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DOI：
10.3109/01677069809108552
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发表时间：
1998-01-01
影响因子：
1.9
通讯作者：
Dowse, H
中科院分区：
文献类型：
--
作者：
Johnson, E;Ringo, J;Dowse, H
果蝇为阐明离子通道在心跳起源和传递中的作用提供了一个极好的模型。我们在这里报告的测试在果蝇中的广泛的突变和药理学代理已知干扰K+，Ca 2+，Na+，和Cl-离子通道，在良好的表征方式。我们发现K+通道是心脏功能的中心。四乙基铵，阻断所有四个钾离子电流，减慢心脏。我们能够区分这些电流。突变慢戳和代理charybdotoxin，这两个影响快速Ca 2+门控K+通道，几乎消除心跳。编码K+通道亚基的Shaker和ether-a-go-go具有中等的、可能是调节性的作用。“OPQ型”Ca 2+通道至关重要。阻断这些通道的ω-芋螺毒素MVIIC实际上使心脏停止。阿米洛利，这可能会影响T型钙通道，没有影响，也没有L型钙阻滞剂维拉帕米和地尔硫卓。温度引起的麻痹E，涉及Na+通道的功能，Na+通道阻断剂河豚毒素和阿米洛利，以及Cl-阻断剂甲凡那酸和尼氟灭酸没有效果。因此，Na+和Cl-通道对心脏功能似乎是不必要的。
Drosophila provides an excellent model for delineating the role of ion channels in the origin and transmission of heartbeat. We report here tests in Drosophila on a wide range of mutations and pharmacological agents known to interfere with K+, Ca2+, Na+, and Cl- ion channels in well-characterized ways. We find K+ channels are central to heart function. Tetraethylammonium, which blocks all four K+ currents, slowed the heart. We were able to distinguish among these currents. The mutation slowpoke and the agent charybdotoxin, both of which affect a fast Ca2+-gated K+ channel, virtually eliminate heartbeat. Shaker and ether-a-go-go, which encode subunits of K+ channels, have moderate, possibly regulatory effects. "OPQ-type" Ca2+ channels are critical. omega-Conotoxin MVIIC, which blocks these channels, virtually stops the heart. Amiloride, which may affect T-type Ca2+ channels, has no effect, nor do the L-type Ca2+ blockers verapamil and diltiazem. temperature induced paralysis E, involved in the function of Na+ channels, the Na+ channel blockers tetrodotoxin and amiloride, and the Cl- blockers mefanamic and niflumic acids have no effect. Na+ and Cl- channels thus appear unnecessary for cardiac function.