Co-assembly of KCNQ4 (Kv7.4) and Erg (Kv11) potassium channels as molecular basis of the characteristic outer hair cell current IK,n

• Applicant: Dr. Michael Leitner
• Subject Area: Anatomy and Physiology
• Term: from 2015 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 279586168

The extraordinary acuity of mammalian hearing critically depends on active cochlear amplification through ultrafast somatic length changes of outer hair cells. Because these length changes are driven by membrane potential variations, sensitivity directly relies on ultrafast sound-induced receptor potentials. In outer hair cells, such potential changes are facilitated by the unique voltage-dependence of the potassium (K+) current IK,n. Thus, the unusual characteristics of IK,n are a biophysical prerequisite for cochlear amplification. KCNQ4 (Kv7.4) K+ channel subunits have been identified as molecular components of IK,n, but sole contribution of KCNQ4 does not explain the properties of the native current. Probably, yet unknown interaction partners of KCNQ4 produce IK,n in outer hair cells. We present a research project based on a targeted candidate approach to elucidate the molecular constituents of IK,n. We identified KCNQ4-atypical features of IK,n that were highly reminiscent of the distinct family of voltage-dependent Erg (Kv11) K+ channels. Erg subunits colocalised closely with KCNQ4 in outer hair cells and surprisingly co-assembled into the same ion channel complex. Accordingly, we hypothesise that interaction of Erg subunits with KCNQ4 determines the extraordinary properties of IK,n. We propose a working programme to test this potential interaction of KCNQ4 and Erg channel subunits. Ultimately, using cutting-edge genetic techniques we will generate Erg protein knock-out mice to elucidate functional importance of Erg channels for signal processing in the cochlea.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1608: Ultrafast and Temporally Precise Information Processing: Normal and Dysfunctional Hearing
• International Connection: Austria