Inhibition of connexin 43 induces hearing loss in postnatal mice.

Abstract

Connexin 43 (Cx43) is the most ubiquitously expressed member of the family of connexins, constituting gap junctions and mediating cell communication, still its role in hearing loss has been little studied. Immunohistochemistry was used to detect the expression pattern of Cx43. Spiral ganglia neurons (SGNs) and Corti co-culture were utilized to assay the re-innervation of hair cells by newborn SGNs. Gap19 was utilized to inhibit Cx43 hemichannels. Auditory brainstem responses (ABR) and endocochlear potential (E.P.) were measured to confirm the hearing loss. The expression of Cx43 in P14 mice was higher than in P0 and P28 (adult) mice, the earlier time point coinciding with the early inner ear development. Additionally, the growth and synapse generation of fibers were inhibited after Gap 19 treatment of the co-cultures of the Corti and SGNs from newborn mice. Furthermore, the inhibition of Cx43 could increase the ABR threshold and decrease E.P. level in postnatal mice, whereas such an effect was not observed in adult mice. The function of Cx43 is critical during the early development of mouse cochlea but is dispensable in adult mice.