Expression of an inwardly rectifying K⁺ channel, Kir5.1, in specific types of fibrocytes in the cochlear lateral wall suggests its functional importance in the establishment of endocochlear potential

Abstract

Cochlear endolymph contains 150 mm K+ and has a highly positive potential of approximately +80 mV. The specialized ionic composition and high potential in endolymph are essential for hearing and maintained by circulation of K+ from perilymph to endolymph through the cochlear lateral wall. Various types of K+ channel such as Kir4.1 and KCNQ1/KCNE1 are expressed in stria vascularis of the lateral wall and play essential roles in K+ circulation. In this study, we examined a distribution of another K+ channel, Kir5.1, and found it specifically expressed in the spiral ligament of the cochlear lateral wall. Specific immunoreactivity for Kir5.1 was detected in type II, IV and V fibrocytes of the ligament and spiral limbus, all of which are directly involved in K+ circulation. Kir5.1 was not found in either type I or III fibrocytes. Although Kir5.1 assembles with Kir4.1 to form a functional Kir channel in renal epithelia and retinal Müller cells, double-immunolabelling revealed that they were expressed in distinct regions in the cochlea lateral wall, i.e. Kir4.1 only in stria vascularis vs. Kir5.1 in spiral ligament. During development, the expression of Kir5.1 subunits started significantly later than Kir4.1 and was correlated with the 'rapid' phase of the elevation of endocochlear potential (EP). Kir5.1 and Kir4.1 channel-subunits may therefore play distinct functional roles in K+ circulation in the cochlear lateral wall.

Cisplatin Cytotoxicity of Auditory Cells Requires Secretions of Proinflammatory Cytokines via Activation of ERK and NF-κB

“…by Type II and IV fibrocytes in the ligament (Hibino et al 2004;Kikuchi et al 1995), which abundantly expresses Na + ,K + -ATPase and Na + ,K + ,2Cl _ cotransporter (Hibino et al 2004). Through these types of fibrocytes, potassium enters the stria vascularis via connective tissue gap junctions and potassium channels (Hibino et al 2004;Kikuchi et al 1995).…”

“…Through these types of fibrocytes, potassium enters the stria vascularis via connective tissue gap junctions and potassium channels (Hibino et al 2004;Kikuchi et al 1995). The strial marginal cells then return potassium to the scala media, where it is once again available to sensory hair cells.…”

Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes

“…Briefly, the bodies of adult female C57BL/6 mice, which were deeply anesthetized with pentobarbital sodium (100 mg/kg), were perfused from their left ventricle with 4% paraformaldehyde, 0.1 M sodium phosphate, pH 7.4, and the brains were isolated. The procedures for double-immunolabeling of slice sections have been previously published (14,16,30,31). In short, cryosections of brain (12 m) were at first incubated with antiKir5.1 (4 g/ml; Figs.…”

Postnatal developmental expression of the PDZ scaffolds Na+-H+ exchanger regulatory factors 1 and 2 in the rat cochlea

“…We have recently identified NHERF-1 protein co-immunoprecipitating with TASK-1 (unpublished observations), a developmentally regulated PDZ-domain-containing two-pore domain K + channel strongly expressed in radial and Bergmann glia in the central nervous system (Kanjhan et al 2004b) and in the cochlea (Deiters and pillar cells and neuroglia; Kanjhan et al 2004a). Cochlear glial cells, including spiral ganglion satellite cells, have previously been shown to express a number of Kir channels, e.g., Kir4.1 (Hibino et al 2004). NHERF-1 and ERM proteins have also been reported in polarized Schwann cell processes where they have been implicated in the formation of the nodes of Ranvier (Gatto et al 2003).…”

“…The rationale for the current study comes from the finding that the cochlea contains a number of proteins known to interact with NHERFs, plus numerous other proteins that have PDZ domains that could potentially interact with NHERFs. These cochlear proteins include NHE3 (Bond et al 1998), the ERM family (Kitajiri et al 2004), actin (Geal-Dor et al 1993;Nishida et al 1998), myosin (Boeda et al 2002;Johnson et al 2003;Mburu et al 2003;Kitajiri et al 2004;Belyantseva et al 2005;Kikkawa et al 2005), NBC3 (Bok et al 2003), P2Y1 (Teixeira et al 2000), β-adrenergic receptors (Fauser et al 2004), the vacuolar proton pump v-H + -ATPase (Stankovic et al 1997), Na + -K + ATPase (Ichimiya et al 1994;Erichsen et al 1996), growth factor receptors (Pickles and van Heumen 1997), glucocorticoid receptors (Erichsen et al 1996), TASK-1 background K + channels (Kanjhan et al 2004a), inwardly rectifying K + channels Kir1.1 (ROMK1) (Glowatzki et al 1995), Kir4.1 and Kir5.1 (Hibino et al 2004), aquaporin-4 (Mhatre et al 2002), glutamate transporter GLAST (Furness and Lehre 1997), and plasma membrane Ca 2+ -ATPase (Ichimiya et al 1994;Dumont et al 2001). …”