Gap-junctional channel and hemichannel activity of two recently identified connexin 26 mutants associated with deafness.

FIORI MC; DEL RIO R; ELGOYHEN AB; DALAMÓN, VIVIANA KARINA; OLIVA CA; CANAN J; RETAMAL MA; FIGUEROA VA; GONZALEZ W; ALTENBERG GA

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY

SPRINGER

Lugar: Berlin; Año: 2016 vol. 468 p. 909 - 918

0031-6768

Gap-junction channels (GJCs) are formed by head-to-head association of two hemichannels (HCs, connexin hexamers). HCs and GJCs are permeable to ions and hydrophilic molecules of up to Mr ~1 kDa. Hearing impairment of genetic origin is common, and mutations of connexin 26 (Cx26) are its major cause. We recently identified two novel Cx26 mutations in hearing-impaired subjects, L10P and G109V. L10P forms functional GJCs with slightly altered voltage dependence and HCs with decrease ATP/cationic dye selectivity. G109V does not form functional GJCs, but forms functional HCs with enhanced extracellular Ca2+ sensitivity and subtle alterations in voltage dependence and ATP/cationic dye selectivity. Deafness associated with G109V could result from decreased GJCs activity, whereas deafness associated to L10P may have a more complex mechanism that involves changes in HC permeability.