Restoration of ion channel function in deafness-causing KCNQ4 mutants by synthetic channel openers.

ABSTRACT:

Background and purpose

DFNA2 is a frequent hereditary hearing disorder caused by loss-of-function mutations in the voltage-gated potassium channel KCNQ4 (Kv7.4). KCNQ4 mediates the predominant K(+) conductance, I(K,n) , of auditory outer hair cells (OHCs), and loss of KCNQ4 function leads to degeneration of OHCs resulting in progressive hearing loss. Here we explore the possible recovery of channel activity of mutant KCNQ4 induced by synthetic KCNQ channel openers.

Experimental approach

Whole cell patch clamp recordings were performed on CHO cells transiently expressing KCNQ4 wild-type (wt) and DFNA2-relevant mutants, and from acutely isolated OHCs.

Key results

Various known KCNQ channel openers robustly enhanced KCNQ4 currents. The strongest potentiation was observed

SUBMITTER: Leitner MG 

PROVIDER: S-EPMC3413860 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature