Effect of 2-Aminoethoxydiphenyl Borate (2-APB) on Heart Rate and Relation with Suppressed Calcium-Activated Potassium Channels: Larval Drosophila Model

Nicole Hensley, Elizabeth R. Elliott, Maya O. Abul-Khoudoud, R. Cooper
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Abstract

Cardiac contractile cells depend on calcium in order to function. Understanding the regulation of calcium influx, efflux, and release from the sarcoplasmic reticulum is essential. The focus of this investigation is to address how a reduction of functional Ca2+-activated K+ (KCa) channels, via a mutational line, might impact the heart rate in larva when the SER is also modulated through Ca2+ loading and stimulation. The larval heart tube is exposed in situ and flushed with saline. With a known saline composition, a potential therapeutic pharmacological agent, 2-Aminoethyl diphenylborinate (2-APB), was examined for its effect on heart rate, as well as to determine the contribution from KCa channels. In this study, it was determined that mutation in the K(Ca) channel (i.e., Slo) showed a different trend than the wild-type CS strain. Exposure to high concentrations of 50 µM 2-APB decreased heart rate in the Slo strain and increased it in the wild-type CS strain. Serotonin increased heart rate in both thapsigargin- and 2-APB-treated larvae, with no significant difference between the strains.
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2-氨基乙氧基二苯硼酸酯(2-APB)对心率的影响及其与抑制钙活化钾通道的关系:幼虫果蝇模型
心脏收缩细胞依靠钙来发挥功能。了解钙从肌浆网流入、流出和释放的调控是必要的。本研究的重点是解决如何减少功能Ca2+激活的K+ (KCa)通道,通过突变线,可能会影响幼虫的心率,当SER也通过Ca2+负载和刺激调节。在原位暴露幼体的心管并用生理盐水冲洗。在已知的生理盐水成分下,研究了一种潜在的治疗药物,2-氨基乙基二苯硼酸盐(2-APB)对心率的影响,并确定了KCa通道的作用。在本研究中,确定了K(Ca)通道(即Slo)的突变趋势与野生型CS菌株不同。暴露于高浓度的50µM 2-APB中,slow菌株的心率降低,而野生型CS菌株的心率升高。血清素增加了thapsigargin和2- apb处理的幼虫的心率,菌株之间没有显著差异。
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