Developmental failure in cochlear hair cells from mouse models of Usher syndrome and the identification of an acid sensitive ionic current in Inner and Outer hair cells

摘要

Inner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea. I employed the whole-cell patch-clamp technique to study voltage responses and ionic currents of IHCs in mice bearing mutations in hair bundle proteins. These mutations, all associated with Usher syndrome, lead to structural and functional defects of the mechanosensory hair bundle. I observed developmental failure in the electrical properties of IHCs from these mutants: a continuation of neonatal spiking instead of the graded receptor potentials seen in control adult IHCs. Voltage-clamp recordings revealed the main cause as the absence of the adult fast potassium (IK,f) current.ududOuter hair cells (OHCs) are required to amplify the travelling wave to be detected by the IHCs. Optical and whole-cell patch clamp techniques in these same mutants were employed to investigate the development of adult OHCs. I observed a developmental failure in the electrical properties of these OHCs, seen by an absence of the potassium current IK,n. Electromotility and the associated non-linear capacitance were however observed, indicating that prestin is expressed in the mutants.ududAcid sensitive ion channels (ASICs) have recently been found to be present within the organ of Corti. Here I present data showing the presence of an acid sensitive ion current in both IHCs and OHCs. ASIC1b knockout mice show a response to changes in the extracellular pH suggesting that the current may be carried through a different channel subtype or that compensatory changes occur. The electrical properties of the IHCs develop to maturity in these mice, however the OHCs appear to remain functionally immature displaying a lack of expression of the IK,n current and electromotily. This lack of electromotile function suggests that ASIC1b may be required either for the function of prestins electromotility or for the targeting of prestin to the cell membrane.