Expression of the LRRC52 γ subunit (γ2) may provide Ca²⁺-independent activation of BK currents in mouse inner hair cells

Mammalian inner hair cells (IHCs) transduce sound into depolarization and transmitter release. Big conductance and voltage- and Ca²⁺-activated K⁺ (BK) channels are responsible for fast membrane repolarization and small time constants of mature IHCs. For unknown reasons, they activate at around -75 mV with a voltage of half-maximum activation (V_half) of -50 mV although being largely insensitive to Ca²⁺ influx. Ca²⁺-independent activation of BK channels was observed by others in heterologous expression systems if γ subunits leucine-rich repeat-containing protein (LRRC)26 (γ1) and LRRC52 (γ2) were coexpressed with the pore-forming BKα subunit, which shifted V_half by -140 and -100 mV, respectively. Using nested PCR, we consistently detected transcripts for LRRC52 but not for LRRC26 in IHCs of 3-wk-old mice. Confocal immunohistochemistry showed synchronous up-regulation of LRRC52 protein with BKα at the onset of hearing. Colocalization of LRRC52 protein and BKα at the IHC neck within ≤40 nm was specified using an insitu proximity ligation assay. Mice deficient for the voltage-gated Ca_v1.3 Ca²⁺ channel encoded by Cacna1d do not express BKα protein. LRRC52 protein was neither expressed in IHCs of BKα nor in IHCs of Ca_v1.3 knockout mice. Together, LRRC52 is a γ2 subunit of BK channel complexes and is a strong candidate for causing the Ca²⁺-independent activation of BK currents at negative membrane potentials in mouse IHCs.-Lang, I., Jung, M., Niemeyer, B. A., Ruth, P., Engel, J. Expression of the LRRC52 γ subunit (γ2) may provide Ca²⁺-independent activation of BK currents in mouse inner hair cells.