Expression of the LRRC52 γ subunit (γ2) may provide Ca2+-independent activation of BK currents in mouse inner hair cells. 2019

Isabelle Lang, and Martin Jung, and Barbara A Niemeyer, and Peter Ruth, and Jutta Engel
Hearing Research, Department of Biophysics and Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, Homburg, Germany.

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 (Vhalf) 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 Vhalf 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 Cav1.3 Ca2+ channel encoded by Cacna1d do not express BKα protein. LRRC52 protein was neither expressed in IHCs of BKα nor in IHCs of Cav1.3 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.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D006199 Hair Cells, Auditory, Inner Auditory sensory cells of organ of Corti, usually placed in one row medially to the core of spongy bone (the modiolus). Inner hair cells are in fewer numbers than the OUTER AUDITORY HAIR CELLS, and their STEREOCILIA are approximately twice as thick as those of the outer hair cells. Auditory Hair Cell, Inner,Auditory Hair Cells, Inner,Cochlear Inner Hair Cell,Cochlear Inner Hair Cells,Hair Cell, Auditory, Inner,Inner Auditory Hair Cell,Inner Auditory Hair Cells,Inner Hair Cells,Cell, Inner Hair,Cells, Inner Hair,Hair Cell, Inner,Hair Cells, Inner,Inner Hair Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015640 Ion Channel Gating The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability. Gating, Ion Channel,Gatings, Ion Channel,Ion Channel Gatings

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