Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, 1800 Christensen Dr, Ames, IA, 50011, USA.
Invert Neurosci. 2020 Aug 16;20(3):12. doi: 10.1007/s10158-020-00247-1.
Brugia malayi is a human filarial nematode parasite that causes lymphatic filariasis or 'elephantiasis' a disfiguring neglected tropical disease. This parasite is a more tractable nematode parasite for the experimental study of anthelmintic drugs and has been studied with patch-clamp and RNAi techniques. Unlike in C. elegans however, calcium signaling in B. malayi or other nematode parasites has not been achieved, limiting the studies of the mode of action of anthelmintic drugs. We describe here the development of calcium imaging methods that allow us to characterize changes in cellular calcium in the muscles of B. malayi. This is a powerful technique that can help in elucidating the mode of action of selected anthelmintics. We developed two approaches that allow the recording of calcium signals in the muscles of adult B. malayi: (a) soaking the muscles with Fluo-3AM, promoting large-scale imaging of multiple cells simultaneously and, (b) direct insertion of Fluo-3 using microinjection, providing the possibility of performing dual calcium and electrophysiological recordings. Here, we describe the techniques used to optimize dye entry into the muscle cells and demonstrate that detectable increases in Fluo-3 fluorescence to elevated calcium concentrations can be achieved in B. malayi using both techniques.
班氏丝虫是一种引起淋巴丝虫病或“象皮病”的人类丝虫寄生虫,这是一种使人毁容的被忽视热带病。这种寄生虫是一种更易于研究驱虫药物的线虫寄生虫,已经使用膜片钳和 RNAi 技术进行了研究。然而,与秀丽隐杆线虫不同的是,尚未在班氏丝虫或其他线虫寄生虫中实现钙信号,这限制了对驱虫药物作用模式的研究。我们在这里描述了钙成像方法的发展,这些方法使我们能够描述班氏丝虫肌肉中细胞钙的变化。这是一种强大的技术,可以帮助阐明选定驱虫药物的作用模式。我们开发了两种方法,可以记录成年班氏丝虫肌肉中的钙信号:(a)用 Fluo-3AM 浸泡肌肉,促进同时对多个细胞进行大规模成像,以及(b)使用微注射直接插入 Fluo-3,提供同时进行钙和电生理记录的可能性。在这里,我们描述了优化染料进入肌肉细胞的技术,并证明可以使用这两种技术在班氏丝虫中实现对升高的钙浓度的 Fluo-3 荧光的可检测增加。