The Membrane Properties of Cochlear Root Cells are Consistent with Roles in Potassium Recirculation and Spatial Buffering

Abstract

Auditory transduction, amplification, and hair cell survival depend on the regulation of extracellular [K + ] in the cochlea. K + is removed from the vicinity of sensory hair cells by epithelial cells, and may be distributed through the epithelial cell syncytium, reminiscent of "spatial buffering" in glia. Hypothetically, K + is then transferred from the epithelial syncytium into the connective tissue syncytium within the cochlear lateral wall, enabling recirculation of K + back into endolymph. This may involve secretion of K + from epithelial root cells, and its re-uptake via transporters into spiral ligament fibrocytes. The molecular basis of this secretion is not known. Using a combination of approaches we demonstrated that the resting conductance in guinea pig root cells was dominated by K + channels, most likely composed of the Kir4.1 subunit. Dye injections revealed extensive intercellular gap junctional coupling, and delineated the root cell processes that penetrated the spiral ligament. Following uncoupling using 1-octanol, individual cells had Ba 2+ -sensitive weakly rectifying currents. In the basal (high-frequency encoding) cochlear region K + loads are predicted to be the highest, and root cells in this region had the largest surface area and the highest current density, consistent with their role in K + secretion. Kir4.1 was localized within root cells by immunofluorescence, and specifically to root cell process membranes by immunogold labeling. These results support a role for root cells in cochlear K + regulation, and suggest that channels composed of Kir4.1 subunits may mediate K + secretion from the epithelial gap junction network.

Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea

“…The patterns of dye transfer in the undamaged fully mature organ of Corti from hearing animals resembled that previously described for rats at the onset of hearing (P12) [34]. When Lucifer Yellow (LY), which can pass through gap channels composed of Cx26 but not those which contain Cx30 [35], together with neurobiotin (NBN), which can pass through gap junction channels of any composition, were co-injected into an individual Deiters' cell LY was retained within the cell whereas NBN spread to other Deiters' cells and outwards to the outer sulcus. It also spread inwards to the outer pillar cell, but it did not pass to the inner pillar cell (Fig.…”

Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

“…However, mutations in KCNJ10 itself have also been linked directly to Pendred syndrome (Yang et al, 2009). Interestingly, KCNJ10 has also been described in the root cells of the outer sulcus, both in the adult rodent and human cochlea (Jagger et al, 2010; Eckhard et al, 2012). Also, the expression pattern of KCNJ10 that we observed in the outer sulcus during cochlear development matches the known expression pattern of PENDRIN in the outer sulcus of the adult mouse cochlea (Royaux et al, 2003; Wangemann et al, 2004).…”

Molecular Mechanisms of EAST/SeSAME Syndrome Mutations in Kir4.1 (KCNJ10)

“…Kir4.1 is predominant in Müller glial cells, where it contributes to normal retinal physiology (13)(14)(15)(16)(17)(18), and in satellite glial cells of sensory ganglia (19). Kir4.1 channels in oligodendrocytes are critical for myelination (20,21), and in various cell types of the inner ear they play a role in K ϩ regulation and generation of the endocochlear potential, essential for normal development of the cochlea and audition (22)(23)(24)(25).…”