Mian Zu1,2,3,4, Wei-Wei Guo1,2,3,4, Tao Cong1,2,3,4, Fei Ji1,2,3,4, Shi-Li Zhang5, Yue Zhang1,2,3,4, Xin Song1,2,3,4, Wei Sun6, David Z Z He7, Wei-Guo Shi8, Shi-Ming Yang9,10,11,12. 1. College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China. 2. National Clinical Research Center for Otolaryngologic Diseases, Beijing, China. 3. Key Lab of Hearing Science, Ministry of Education, Beijing, China. 4. Beijing Key Lab of Hearing Impairment for Prevention and Treatment, Beijing, China. 5. Clinical Hearing Center of Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. 6. Department of Communicative Disorders and Sciences, Center for Hearing and Deafness, The State University of New York at Buffalo, Buffalo, NY, USA. 7. Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, 68178, USA. 8. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China. shiwg1988@126.com. 9. College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China. yangsm301@263.net. 10. National Clinical Research Center for Otolaryngologic Diseases, Beijing, China. yangsm301@263.net. 11. Key Lab of Hearing Science, Ministry of Education, Beijing, China. yangsm301@263.net. 12. Beijing Key Lab of Hearing Impairment for Prevention and Treatment, Beijing, China. yangsm301@263.net.
Abstract
BACKGROUND: The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice. RESULTS: Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds. CONCLUSIONS: These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.
BACKGROUND: The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice. RESULTS: Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds. CONCLUSIONS: These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.
Authors: Jianying Huang; Carlos G Vanoye; Alison Cutts; Y Paul Goldberg; Sulayman D Dib-Hajj; Charles J Cohen; Stephen G Waxman; Alfred L George Journal: J Clin Invest Date: 2017-05-22 Impact factor: 14.808
Authors: Brikha R Shrestha; Chester Chia; Lorna Wu; Sharon G Kujawa; M Charles Liberman; Lisa V Goodrich Journal: Cell Date: 2018-08-02 Impact factor: 41.582