Resistance to neomycin ototoxicity in the extreme basal (hook) region of the mouse cochlea.

Aminoglycoside ototoxicity results in permanent loss of the sensory hair cells in the mammalian cochlea. It usually begins at the basal turn causing high-frequency hearing loss. Here we describe previously unreported resistance of hair cells to neomycin ototoxicity in the extreme basal (hook) region of the developing cochlea of the C57BL/6 mouse. Organ of Corti explants from mice at postnatal day 3 were incubated (37 °C, 5% CO2) in normal culture medium for 19.5 h prior to and after exposure to neomycin (1 mM, 3 h). To study neomycin uptake in the hair cells, cochlear explants were incubated with Neomycin Texas-red (NTR) conjugate. As expected, exposure to neomycin significantly reduced the survival of inner (IHC) and outer hair cells (OHC). IHC survival rate was high in the apical segment and low in the basal segment. OHC were well preserved in the apical and hook regions, with substantial OHC loss in the basal segment. The NTR uptake study demonstrated that the high survival rate in the extreme basal turn OHC was associated with low NTR uptake. Treatment with a calcium chelator (BAPTA), which disrupts the opening of mechanoelectrical (MET) transduction channels, abolished or reduced NTR uptake in the hair cells throughout the cochlea. This confirmed the essential role of MET channels in neomycin uptake and implied that the transduction channels could be impaired in the hook region of the developing mouse cochlea, possibly as a result of the cadherin 23 mutation responsible for the progressive deafness in C57BL/6 mice.

Echinococcus multilocularis (Cestoda, Cyclophyllidea, Taeniidae): origin, differentiation and functional ultrastructure of the oncospheral tegument and hook region membrane.

Both the oncospheral tegument and the hook region membrane (HRM) of Echinococcus multilocularis hexacanths originate from a syncytial binucleate complex that appears in the early stage of morphogenesis and organogenesis of the hexacanth larva. The primordium of this binucleate complex forms a binucleate syncytial cap or "calotte" situated beneath the inner envelope at one pole of the developing embryo. During oncospheral differentiation, the binucleate perikaryon of the syncytial cap is sunk progressively deeper into the central part of the embryo, but remains always connected with the distal cytoplasm by a tendrillar cytoplasmic connection or bridge. Following migration or sinking of the binucleate perikaryon, numerous cytoplasmic vesicles appear in the distal cytoplasm. These vesicles fuse progressively together and form a single large cavity or lacuna. The walls of this cavity are becoming at this point the walls of two delaminated layers: (1) the distal anucleated cytoplasmic layer is transformed into the oncospheral tegument and (2) the proximal thin cytoplasmic layer is transformed into the "hook region membrane". This delamination of the initially compact layer of distal cytoplasm into two layers seems to be closely associated with differentiation of oncospheral hooks, the elongating blades of which protrude progressively into a newly formed cavity. The pressure of hook blades on the hook region membrane appears to facilitate its further separation from the basal layer of distal cytoplasm which is transformed into the peripheral layer of oncospheral tegument. In the mature oncosphere, the surface of this peripheral layer forms a regular brush border of cytoplasmic processes or microvilli and represents the true body covering of the hexacanth. The very thin cytoplasmic connection between the peripheral layer of tegument and binucleate perikaryon appears only very seldom in the ultrathin sections as a narrow cytoplasmic strand and has a plasma membrane that is reinforced by a single row of cortical microtubules. The HRM covers only one pole of the oncosphere and is attached to the oncosphere surface. The HRM is clearly visible in the mature oncosphere and is draped over the hook blades, the sharp points of which are protected by moderately electron-dense caps. Comparison of the above morphology with that of TEM study of the tegument of adult cestodes shows a great similarity as well as homology in the body covering of both larval and adult cestodes.

The HOOK region of ß subunits controls gating of voltage-gated Ca2+ channels by electrostatically interacting with plasma membrane.

Recently, we showed that the HOOK region of the ß2 subunit electrostatically interacts with the plasma membrane and regulates the current inactivation and phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of voltage-gated Ca2+ (CaV) 2.2 channels. Here, we report that voltage-dependent gating and current density of the CaV2.2 channels are also regulated by the HOOK region of the ß2 subunit. The HOOK region can be divided into 3 domains: S (polyserine), A (polyacidic), and B (polybasic). We found that the A domain shifted the voltage-dependent inactivation and activation of CaV2.2 channels to more hyperpolarized and depolarized voltages, respectively, whereas the B domain evoked these responses in the opposite directions. In addition, the A domain decreased the current density of the CaV2.2 channels, while the B domain increased it. Together, our data demonstrate that the flexible HOOK region of the ß2 subunit plays an important role in determining the overall CaV channel gating properties.

[Topographic anatomy of the hook region and its significance for the choice of the surgical technique for the cochlear implantation]. / Topograficheskaia anatomiia oblasti 'rybolovnogo kriuchka' i ee znachenie pri vybore khirurgicheskoi tekhniki kokhlearnoi implantatsii.

The mode of the introduction of the active electrode of a cochlear implant into the cochlea remains a key issue as far as cochlear implantation is concerned. Especially much attention has recently been given to the relationship between the anatomical features of the basal region of the cochlea (the so-called 'fish hook') and the possibility to approach it. We have undertaken the attempt to optimize the approach to the tympanic canal (scala tympanica) of the cochlea with a view to reducing to a minimum the risk of an injury to the cochlear structures in the course of cochlear implantation. A total of 35 cadaveric temporal bones were examined to measure the fine structures of the hook region and evaluate the risk of their damages associated with various approaches to the tympanic canal.