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Joseph Santos-Sacchi, Winston Tan
The voltage-dependent protein SLC26a5 (prestin) underlies outer hair cell electromotility (eM), which is responsible for cochlear amplification in mammals. The electrical signature of eM is a bell-shaped nonlinear capacitance (NLC), deriving from prestin sensor-charge (Qp ) movements, which peaks at the membrane voltage, Vh , where charge is distributed equally on either side of the membrane. Voltage dependencies of NLC and eM differ depending on interrogation frequency and intracellular chloride, revealing slow intermediate conformational transitions between anion binding and voltage-driven Qp movements...
June 13, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Aoshuang Chang, Cuixian Li, Jianfeng Huang, Wenlu Pan, Yinghong Tian, Jie Tang
The outer hair cell is one of the two types of sensory hair cells in the mammalian cochlea. They alter their cell length with the receptor potential to amplify the weak vibration of low-level sound signal. The morphology and electrophysiological property of outer hair cells (OHCs) develop in early postnatal ages. The maturation of outer hair cell may contribute to the development of the auditory system. However, the process of OHCs development is not well studied. This is partly because of the difficulty to measure their function by an electrophysiological approach...
May 24, 2018: Journal of Visualized Experiments: JoVE
Aoshuang Chang, Peng Chen, Shasha Guo, Nana Xu, Wenlu Pan, Hongzheng Zhang, Cuixian Li, Jie Tang
The auditory function develops and matures after birth in many mammalian species. After hearing onset, environmental sounds exert profound and long-term effects on auditory functions. However, the effects of the acoustic environment on the functional development of the peripheral auditory system, especially the cochlear sensory hair cells, are still unclear. In the present study, we exposed mouse pups to frequency-enriched acoustic environments in postnatal days 0-14. The results indicated that the acoustic environment significantly decreased the threshold of the auditory brainstem response in a frequency-specific manner...
2018: Neural Plasticity
Makoto F Kuwabara, Koichiro Wasano, Satoe Takahashi, Justin Bodner, Tomotaka Komori, Sotaro Uemura, Jing Zheng, Tomohiro Shima, Kazuaki Homma
Pendrin and prestin belong to the solute carrier 26 (SLC26) family of anion transporters. Prestin is unique among the SLC26 family members in that it displays voltage-driven motor activity (electromotility) and concurrent gating currents that manifests as nonlinear cell membrane electrical capacitance (NLC). Although the anion transport mechanism of the SLC26 proteins has begun to be elucidated, the molecular mechanism of electromotility, which is thought to be evolved from an ancestral ion transport mechanism, still remains largely elusive...
May 18, 2018: Journal of Biological Chemistry
Chao Li, Yilai Shu, Guangqin Wang, He Zhang, Ying Lu, Xiang Li, Gen Li, Lei Song, Zhiyong Liu
Precise mouse genetic studies rely on specific tools that can label specific cell types. In mouse cochlea, previous studies suggest that vesicular glutamate transporter 3 (vGlut3), also known as Slc17a8, is specifically expressed in inner hair cells (IHCs) and loss of vGlut3 causes deafness. To take advantage of its unique expression pattern, here we generate a novel vGlut3-P2A-iCreER knockin mouse strain. The P2A-iCreER cassette is precisely inserted before stop codon of vGlut3, by which the endogenous vGlut3 is intact and paired with iCreER as well...
July 2018: Hearing Research
Mohammad N Kayyali, Julian R A Wooltorton, Andrew J Ramsey, Mei Lin, Tiffany N Chao, Andrew Tsourkas, Bert W O'Malley, Daqing Li
Hearing loss is the most prevalent sensory disability worldwide and may be caused by age, drugs or exposure to excessive noise. We have previously developed a minimally-invasive nanohydrogel drug delivery system that successfully delivers nanoparticles into the inner ear. We have substantially extended this technique by functionalizing the nanoparticles and introducing a targeting peptide which recognizes prestin, a transmembrane electromotile protein uniquely expressed in outer hair cells (OHCs) of the inner ear...
June 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
T Chen, W Zhang, Y Liang, Q Li, C Yang, Y X Yuan, M L Ban
Objective: To investigate the effect of melatonin on the expression of prestin protein in the inner ear of mice following a single dose radiation therapy, so as to provide the basis for the mechanism study of radiation induced inner ear injury and its prevention. Methods: Sixty 4-week-old male mice were randomly divided into six groups, including the control group (A group), 50 mg/kg MLT group (B group), 5 mg/kg MLT group (C group), 50 mg/kg MLT + radiotherapy group (D group), 5 mg/kg MLT+ radiotherapy group (E group), and 16 Gy radiotherapy group (F group)...
February 7, 2018: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
X Luo, J Y Wang, F L Zhang, Y Xia
Objective: To explore the regulation and mechanism of Prestin protein by identifying the proteins interacted with Prestin in cochlear outer hair cell(OHC) and analyzing their biological function. Methods: Co-immunoprecipitation combined mass spectrometry technology was used to isolate and identify the proteins interacted with Prestin protein of OHC, bioinformatics was used to construct Prestin protein interaction network. The proteins interacted with Prestin in OHC of guinea pig were determined by matching primary interaction mass spectrometry with protein interaction network, and annotated their functions...
January 7, 2018: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Hui Nam, John J Guinan
Recent cochlear mechanical measurements show that active processes increase the motion response of the reticular lamina (RL) at frequencies more than an octave below the local characteristic frequency (CF) for CFs above 5 kHz. A possible correlate is that in high-CF (>5 kHz) auditory-nerve (AN) fibers, responses to frequencies 1-3 octaves below CF ("tail" frequencies) can be inhibited by medial olivocochlear (MOC) efferents. These results indicate that active processes enhance the sensitivity of tail-frequency RL and AN responses...
December 14, 2017: Hearing Research
James Naples, Robert Cox, Gregory Bonaiuto, Kourosh Parham
Objective To evaluate (1) whether changes in serum prestin aid in early detection of cisplatin ototoxicity, (2) the role of diltiazem as an otoprotectant, and (3) whether prestin levels are sensitive to effects of diltiazem. Study Design Experimental animal study. Setting Translational research laboratory. Subjects Twenty female guinea pigs. Methods Two groups of 10 guinea pigs were used. The relationship between serum prestin levels and auditory brainstem response (ABR) thresholds was compared between the groups...
March 2018: Otolaryngology—Head and Neck Surgery
(no author information available yet)
Background/aim: Activity of the prestin gene may have a role in the pathogenesis of salicylate-induced ototoxicity. We investigated DNA methylation for prestin gene exon 1 in salicylate-injected guinea pigs.Materials and methods: Fifteen guinea pigs (30 ears) underwent audiological evaluation including 1000 Hz probe-tone tympanometry and a distortion product otoacoustic emission (DPOAE) test. The animals were randomly divided into three groups. Groups 2 (8 ears) and 3 (14 ears) were injected with intramuscular saline and sodium salicylate (200 mg/kg), respectively twice daily for 2 weeks...
November 13, 2017: Turkish Journal of Medical Sciences
Benjamin Liba, James Naples, Elizabeth Bezyk, Charlene Campbell, Michael Mei, Kourosh Parham
HYPOTHESIS: There are temporal changes in the outer-hair-cell-specific protein, prestin, in the blood after administration of low-dose cisplatin. METHODS: Two rodent models of ototoxicity were used. After control and baseline data collection, mice (n = 30) and guinea pigs (n = 10), respectively, were treated with cisplatin at 8 mg/kg. Auditory brainstem responses were recorded on Days 1, 3, 7, and 14 after treatment. Five mice were sacrificed at each time point and serum samples were obtained...
December 2017: Otology & Neurotology
Celio Ferreira, Katharina Prestin, Janine Hussner, Uwe Zimmermann, Henriette E Meyer Zu Schwabedissen
Genome wide association studies revealed single nucleotide polymorphisms (SNP) located within the promoter of PDZ domain containing protein 1 (PDZK1) to be associated with serum uric acid levels. Since modulation of transporters and particularly of membrane proteins involved in uric acid handling by PDZK1 has previously been reported, the aim of this study was to analyze the impact of the polymorphisms rs1967017, rs1471633, and rs12129861 on promoter activity and thereby transcription of PDZK1. Cell-based reporter gene assays showed transactivation of the PDZK1-promoter by triiodothyronine mediated by thyroid hormone receptors (THR) α and β...
February 5, 2018: Molecular and Cellular Endocrinology
Robert Fettiplace
Sound pressure fluctuations striking the ear are conveyed to the cochlea, where they vibrate the basilar membrane on which sit hair cells, the mechanoreceptors of the inner ear. Recordings of hair cell electrical responses have shown that they transduce sound via submicrometer deflections of their hair bundles, which are arrays of interconnected stereocilia containing the mechanoelectrical transducer (MET) channels. MET channels are activated by tension in extracellular tip links bridging adjacent stereocilia, and they can respond within microseconds to nanometer displacements of the bundle, facilitated by multiple processes of Ca2+-dependent adaptation...
September 12, 2017: Comprehensive Physiology
Abidali Mohamedali, Seong Beom Ahn, Varun K A Sreenivasan, Shoba Ranganathan, Mark S Baker
The evidence that any protein exists in the Human Proteome Project (HPP; protein evidence 1 or PE1) has revolved primarily (although not exclusively) around mass spectrometry (MS) (93% of PE1 proteins have MS evidence in the latest neXtProt release), with robust and stringent, well-curated metrics that have served the community well. This has led to a significant number of proteins still considered "missing" (i.e., PE2-4). Many PE2-4 proteins have MS evidence of unacceptable quality (small or not enough unitypic peptides and unacceptably high protein/peptide FDRs), transcriptomic, or antibody evidence...
December 1, 2017: Journal of Proteome Research
Katharina Prestin, Maria Olbert, Janine Hussner, Henry Völzke, Henriette E Meyer Zu Schwabedissen
Small heterodimer partner 1 (SHP1, NR0B2) is a member of the superfamily of nuclear receptors (NRs). Even if this orphan receptor, unlike other NRs, lacks the DNA-binding domain, it is capable of regulating transcription by repressing the activity of other NRs by direct protein-protein interaction. Accordingly, SHP1 is part of negative feedback loops of the transcriptional regulation of genes involved in drug metabolism and various metabolic pathways including bile acid and glucose homeostasis. Although it is known that several interacting partners of SHP1 also modulate its expression, there is little information about genetic variability of this regulatory mechanism...
November 2017: Pharmacogenetics and Genomics
Guillaume Duret, Fred A Pereira, Robert M Raphael
The motor protein prestin is a member of the SLC26 family of anion antiporters and is essential to the electromotility of cochlear outer hair cells and for hearing. The only direct inhibitor of electromotility and the associated charge transfer is salicylate, possibly through direct interaction with an anion-binding site on prestin. In a screen to identify other inhibitors of prestin activity, we explored the effect of the non-steroid anti-inflammatory drug diflunisal, which is a derivative of salicylate. We recorded prestin activity by whole-cell patch clamping HEK cells transiently expressing prestin and mouse outer hair cells...
2017: PloS One
Katharina Prestin, Janine Hussner, Celio Ferreira, Isabell Seibert, Vivien Breitung, Uwe Zimmermann, Henriette E Meyer Zu Schwabedissen
In the renal proximal tubule the secretion and reabsorption of glomerularly filtrated compounds is realized by a functional network of uptake and efflux transporters. The activity and localization of several transporters expressed at the apical tubular membrane are regulated by the membrane-associated protein PDZ domain-containing 1 (PDZK1). We aimed to characterize the transcriptional regulation of this modulator of renal transport. Coexpression analyses of PDZK1 and putative regulators were performed using human kidney samples...
October 1, 2017: American Journal of Physiology. Renal Physiology
Bernd Fritzsch, Karen L Elliott
All craniate chordates have inner ears with hair cells that receive input from the brain by cholinergic centrifugal fibers, the so-called inner ear efferents (IEEs). Comparative data suggest that IEEs derive from facial branchial motor (FBM) neurons that project to the inner ear instead of facial muscles. Developmental data showed that IEEs develop adjacent to FBMs and segregation from IEEs might depend on few transcription factors uniquely associated with IEEs. Like other cholinergic terminals in the peripheral nervous system (PNS), efferent terminals signal on hair cells through nicotinic acetylcholine channels, likely composed out of alpha 9 and alpha 10 units (Chrna9, Chrna10)...
2017: Frontiers in Cellular Neuroscience
Jun-Ping Bai, Iman Moeini-Naghani, Sheng Zhong, Fang-Yong Li, Shumin Bian, Fred J Sigworth, Joseph Santos-Sacchi, Dhasakumar Navaratnam
Prestin in the lateral membrane of outer hair cells, is responsible for electromotility (EM) and a corresponding nonlinear capacitance (NLC). Prestin's voltage sensitivity is influenced by intracellular chloride. A regulator of intracellular chloride is a stretch-sensitive, non-selective conductance within the lateral membrane, GmetL . We determine that prestin itself possesses a stretch-sensitive, non-selective conductance that is largest in the presence of thiocyanate ions. This conductance is independent of the anion transporter mechanism...
April 19, 2017: Scientific Reports
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