Calcium waves, connexin permeability defects and hereditary deafness

The complex deafness locus DFNB1 contains GJB2, the gene encoding connexin 26 (Cx26) and GJB6, encoding Cx30, the two most abundant connexins in the inner ear (Petit et al., 2001). These connexins may form heteromeric/heterotypic channels in the gap junctions that interconnect cochlear supporting cells. By showing that a specific defect of Cx26 affects metabolic coupling mediated by IP3 we have recently offered a mechanistic explanation for the pathogenesis of deafness due to connexin mutations [1]. Abnormal or impaired connexin function has been linked to several other diseases, including skin disease, peripheral neuropathies, and cataracts [7], thus our data may have a more general impact. Gap junction blockade impairs the spreading of Ca2+ waves and the formation of a functional (glial-like) syncytium in cochlear supporting cells. Wave propagation necessitates also a regenerative mechanism mediated by P2Y receptors [6] and this may constitute a fundamental mechanism by which supporting cells co-ordinate their responses following activation of sensory hair cells by sound.