Hair cells of the vertebrate cochlea are responsible for transducing sound into neuronal output. Mammalian inner hair cells, the subset of hair cells responsible for transducing sound, express a potassium conductance, IK,f, distinguished from other outward currents by its fast rate of activation. A variety of evidence has suggested that a calcium-activated potassium, or BK, channel mediates this current. In amphibians, reptiles, and birds, BK channels in association with other voltage-gated channels are believed to mediate the intrinsic frequency selectivity, or tuning, of the hair cell by an electrical resonance mechanism. In contrast, mammalian IHCs are extrinsically tuned by accessory structures of the cochlea, most notably mechanical properties of the basilar membrane and active processes of the outer hair cells. Thus, the precise role of the IK,f current in mammalian inner hair cells is less clear, although numerous studies have indicated its importance to mammalian hearing. Patch clamp recordings, pharmacology, and immunofluorescence were used to verify that IK,f in mouse inner hair cells is indeed carried by the BK channel. These experiments also revealed, unexpectedly, that these channels have inactivating currents and are located near the apex of the basolateral membrane of the cell away from synaptic sites near the base. To understand the functional contribution of the BK channel alpha and beta subunits in mouse inner hair cells, the morphology, physiology, and functioning of these cells from mice lacking the BKalpha subunit and also from mice lacking both the BKbeta1 and beta4 subunits were characterized. Inner hair cells from BKbeta1/4-/- mice showed wildtype-like BK currents and normal subcellular localization and developmental acquisition of the BK channels. Not surprisingly, then, BKbeta1/4-/- mice had no observable hearing deficit. Surprisingly, however, BKalpha-/- mice also showed no hearing deficit despite the absence of the BKalpha subunit and fast activating potassium current from the inner hair cells as well as the absence of compensatory changes in other transcripts encoding ion channels or transporters in the cochlea. These results suggest that the BKalpha, and also beta1, and beta4 subunits are not essential for normal hearing in mouse.
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