Molecular architecture of the stria vascularis membrane transport system, which is essential for physiological functions of the mammalian cochlea

Abstract

Stria vascularis of the mammalian cochlea transports K(+) to establish the electrochemical property in the endolymph crucial for hearing. This epithelial tissue also transports various small molecules. To clarify the profile of proteins participating in the transport system in the stria vascularis, membrane components purified from the stria of adult rats were analysed by liquid chromatography tandem mass spectrometry. Of the 3236 proteins detected in the analysis, 1807 were membrane proteins. Ingenuity Knowledge Base and literature data identified 513 proteins as being expressed on the 'plasma membrane', these included 25 ion channels and 79 transporters. Sixteen of the former and 62 of the latter had not yet been identified in the stria. Unexpectedly, many Cl(-) and Ca(2+) transport systems were found, suggesting that the dynamics of these ions play multiple roles. Several transporters for organic substances were also detected. Network analysis demonstrated that a few kinases, including protein kinase A, and Ca(2+) were key regulators for the strial transports. In the library of channels and transporters, 19 new candidates for uncloned deafness-related genes were identified. These resources provide a platform for understanding the molecular mechanisms underlying the epithelial transport essential for cochlear function and the pathophysiological processes involved in hearing disorders.

The unique electrical properties in an extracellular fluid of the mammalian cochlea; their functional roles, homeostatic processes, and pathological significance

“…Fourth, some of the channels and transporters in the lateral wall are expected to be functionally affected by Ca 2+ or H + , but the relevance of these ions to the EP is still elusive. This issue may require detailed information on several Ca 2+ or H + transporting molecules detected by our mass spectrometry experiments conducted on strial proteins [ 105 ]. All of these analyses will enable us to improve the NHK model and thereby more precisely describe how the EP and circulation current interplay with each other.…”

“…On the lateral wall, other ion channels and transporters may be expressed and involved in the control of unidirectional K + transport. Candidates have been obtained by our recent mass spectrometry analysis of membrane proteins extracted from rat stria vascularis [ 105 ]. Of 3236 proteins detected in the analysis, 16 ion channels and 62 transporters had not yet been identified in the stria.…”

Increased Dynamics of Tricarboxylic Acid Cycle and Glutamate Synthesis in Obese Adipose Tissue

“…The membrane fraction was prepared for LC/MS measurement as described previously (48). Briefly, the membrane fraction was washed with 8 M urea and then dissolved in dissolution buffer (6 M urea, 0.1 M Na 2 CO 3 , and 0.5% sodium deoxycholate).…”

Electrophysiological properties of strial pericytes and the effect of aspirin on pericyte K+ channels

“…The stria vascularis maintains blood flow stability in the inner ear and also the balanced state of the endocochlear potential (endolymph positive potential), ion transport and endolymph ( 1 , 2 ). Within the microcirculation of the inner ear, the spiral artery of the cochlea has been extensively investigated ( 3 – 11 ).…”

“…The high potassium and endocochlear potentials in the inner lymphatic fluid are established by the vascular lines of the lateral wall of the cochlea ( 1 , 2 ). Following entry into hair cells, K + exits across the basolateral membrane via K + channels and reaches the lateral cochlear wall either by a perilymphatic route or via the gap-junctional network comprising Deiters' cells and epithelial cells on the basilar membrane ( 2 ). K + is subsequently transported across the lateral cochlear wall and finally returned back to endolymph ( 1 , 2 , 12 , 13 ).…”