| First Author | Lingle CJ | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 37 | Pages | 18397-18403 |
| PubMed ID | 31451634 | Mgi Jnum | J:279327 |
| Mgi Id | MGI:6360517 | Doi | 10.1073/pnas.1907065116 |
| Citation | Lingle CJ, et al. (2019) LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells. Proc Natl Acad Sci U S A 116(37):18397-18403 |
| abstractText | The perception of sound relies on sensory hair cells in the cochlea that convert the mechanical energy of sound into release of glutamate onto postsynaptic auditory nerve fibers. The hair cell receptor potential regulates the strength of synaptic transmission and is shaped by a variety of voltage-dependent conductances. Among these conductances, the Ca(2+)- and voltage-activated large conductance Ca(2+)-activated K(+) channel (BK) current is prominent, and in mammalian inner hair cells (IHCs) displays unusual properties. First, BK currents activate at unprecedentedly negative membrane potentials (-60 mV) even in the absence of intracellular Ca(2+) elevations. Second, BK channels are positioned in clusters away from the voltage-dependent Ca(2+) channels that mediate glutamate release from IHCs. Here, we test the contributions of two recently identified leucine-rich-repeat-containing (LRRC) regulatory gamma subunits, LRRC26 and LRRC52, to BK channel function and localization in mouse IHCs. Whereas BK currents and channel localization were unaltered in IHCs from Lrrc26 knockout (KO) mice, BK current activation was shifted more than +200 mV in IHCs from Lrrc52 KO mice. Furthermore, the absence of LRRC52 disrupted BK channel localization in the IHCs. Given that heterologous coexpression of LRRC52 with BK alpha subunits shifts BK current gating about -90 mV, to account for the profound change in BK activation range caused by removal of LRRC52, we suggest that additional factors may help define the IHC BK gating range. LRRC52, through stabilization of a macromolecular complex, may help retain some other components essential both for activation of BK currents at negative membrane potentials and for appropriate BK channel positioning. |
