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.
Digital Object Identifier (DOI)
This work was supported by NIH (R01) DC 05989.
Chen, Jin; Zhu, Yan; Liang, Chun; Chen, Jing; and Zhao, Hong-Bo, "Pannexin1 Channels Dominate ATP Release in the Cochlea Ensuring Endocochlear Potential and Auditory Receptor Potential Generation and Hearing" (2015). Otolaryngology--Head & Neck Surgery Faculty Publications. 1.
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Figure 1: Panx1 deletion in the cochlea in Panx1 conditional knockout (cKO) mice.
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Figure 2: Hearing loss in Panx1 cKO mice.
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Figure 3: Reduction of EP in Panx1 cKO mice.
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Figure 4: CM reduction in Panx1 cKO mice.
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Figure 5: No substantial hair cell degeneration in Panx1 cKO mice.
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Figure 6: Reduction of ATP release in the cochlea in Panx1 cKO mice.
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Figure 7: Schematic drawing of EP generation with Panx1 ATP release in the cochlear lateral wall.