Pannexin1 channels dominate ATP release in the cochlea ensuring endocochlear potential and auditory receptor potential generation and hearing

• Published in: Scientific reports Vol. 5; no. 1; p. 10762
• Main Authors: Chen, Jin, Zhu, Yan, Liang, Chun, Chen, Jing, Zhao, Hong-Bo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.06.2015; Nature Publishing Group
• Subjects: 13/51; 14/19; 14/5; 14/63; 38/1; 38/77; 631/378/87; 631/80; 64/60; 9/30; Adenosine Triphosphate - metabolism; Animals; ATP; Auditory Perception; Cell surface; Clonal deletion; Cochlea; Cochlea - metabolism; Cochlear Microphonic Potentials; Connexins - genetics; Connexins - metabolism; Gene Deletion; Hair; Hair cells; Hair Cells, Auditory - metabolism; Hair Cells, Auditory - pathology; Hearing loss; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - physiopathology; Hearing protection; Humanities and Social Sciences; Isoforms; Mice; Mice, Knockout; multidisciplinary; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Physiology; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep10762

Pannexin1 (Panx1) is a gap junction gene in vertebrates whose proteins mainly function as non-junctional channels on the cell surface. Panx1 channels can release ATP under physiological conditions and play critical roles in many physiological and pathological processes. Here, we report that Panx1 deficiency can reduce ATP release and endocochlear potential (EP) generation in the cochlea inducing hearing loss. Panx1 extensively expresses in the cochlea, including the cochlear lateral wall. We found that deletion of Panx1 in the cochlear lateral wall almost abolished ATP release under physiological conditions. Positive EP is a driving force for current through hair cells to produce auditory receptor potential. EP generation requires ATP. In the Panx1 deficient mice, EP and auditory receptor potential as measured by cochlear microphonics (CM) were significantly reduced. However, no apparent hair cell loss was detected. Moreover, defect of connexin hemichannels by deletion of connexin26 (Cx26) and Cx30, which are predominant connexin isoforms in the cochlea, did not reduce ATP release under physiological conditions. These data demonstrate that Panx1 channels dominate ATP release in the cochlea ensuring EP and auditory receptor potential generation and hearing. Panx1 deficiency can reduce ATP release and EP generation causing hearing loss.