title: Ca2+ homeostasis defects and hereditary hearing loss.
abstract: Ca(2+) acts as a fundamental signal transduction element in inner ear, delivering information about sound, acceleration and gravity through a small number of mechanotransduction channels in the hair cell stereocilia and voltage activated Ca(2+) channels at the ribbon synapse, where it drives neurotransmission. The mechanotransduction process relies on the endocochlear potential, an electrical potential difference between endolymph and perilymph, the two fluids bathing respectively the apical and basolateral membrane of the cells in the organ of Corti. In mouse models, deafness and lack or reduction of the endocochlear potential correlate with ablation of connexin (Cx) 26 or 30. These Cxs form heteromeric channels assembled in a network of gap junction plaques connecting the supporting and epithelial cells of the organ of Corti presumably for K(+) recycle and transfer of key metabolites, for example, the Ca(2+) -mobilizing second messenger IP(3) . Ca(2+) signaling in these cells could play a crucial role in regulating Cx expression and function. Another district where Ca(2+) signaling alterations link to hearing loss is hair cell apex, where ablation or missense mutations of the PMCA2 Ca(2+) -pump of the stereocilia cause deafness and loss of balance. If less Ca(2+) is exported from the stereocilia, as in the PMCA2 mouse mutants, Ca(2+) concentration in endolymph is expected to fall causing an alteration of the mechanotransduction process. This may provide a clue as to why, in some cases, PMCA2 mutations potentiated the deafness phenotype induced by coexisting mutations of cadherin-23 (Usher syndrome type 1D), a single pass membrane Ca(2+) binding protein that is abundantly expressed in the stereocilia.
authors.affiliation: Department of Physics "G. Galilei," University of Padova, Italy. fabio.mammano@unipd.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Mammano
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D034381:Hearing Loss / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism
chemical_list: D017630:Connexins; D000072259:Connexin 26; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium