Molecular Mechanisms of Frequency Discrimination in the Drosophila Ear

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Since the first confirmed evidence of potassium ions crossing the membrane to the first cloned and identified potassium channel from Drosophila melanogaster, the studies of potassium channels have extensively broadened our understanding of physiological activities in living organisms over the past few decades. Identifying the type of potassium channels from its numerous superfamilies in given cells or organs and their corresponding physiological properties is an indispensable step towards clarifying their cellular functions and the mechanism of their regulation. Hearing, as one aspect of basic sensory modalities, plays an essential role in receiving information from the environment and maintaining interspecies communication. Functions of potassium channels in hearing research have also been widely studied, including secretion of K+ ions from stria vascularis of the cochlea, efflux of K+ ions from hair cells for recycling, and electrical tuning modulation of turtle hair cells. In this dissertation, I used Drosophila melanogaster as a study model to further investigate the effects of potassium channels on hearing. Electrical tuning, as the main mechanism to discriminate frequency components from complex sound at frequency < 1 kHz in non-mammalian vertebrates, is a phenomenon with the involvement of multiple voltage-gated K+ channels. To test whether electrical tuning occurs in Drosophila’s ear or not, I recorded the compound action potential response from antenna nerve in wild-type flies and in flies carrying mutated K+ channel alleles. Additionally, the effects of voltage-gated calcium channels (Cav), inward-rectifier potassium channels (Irk1), and motor protein (prestin) were also measured. I found that the chordotonal neurons in the fly’s ear can show an electrical resonance behavior over the tested frequency range, which is modulated by the slo or Shaker channel. It showed that slo or Shaker channel modulates hearing sensation to certain low-frequency ranges. Furthermore, I screened the homologs of potassium channels in Johnston’s Organ (JO) and found that almost all types of potassium channels are present in JO, but with different expression abundance. Meanwhile, some of the tested K+ channels are expressed partly in different sub-population of JO neurons and partly show different subcellular localizations. Judging from the functional studies, none of the twelve tested K+ channels affected electrical signal transduction, but mutant defects were observed in the mechanical amplification that, based on the severeness of the amplification defects, can be categorized into three groups according to the influenced amplification gain value: no effect (SK, Irk2, Shaw, and Shal channels), mildly impaired (slo, Irk1, Shaker, and KCNQ), and severely impaired (Shab). This thesis provides insight into how the K+ channels perform and the molecular mechanisms of frequency discrimination in Drosophila hearing.