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Fast inhibitory synaptic transmission in the central nervous system is mediated by ionotropic GABA or glycine receptors. Auditory outer hair cells present a unique inhibitory synapse that uses a Ca2+-permeable excitatory acetylcholine receptor to activate a hyperpolarizing potassium current mediated by small conductance calcium-activated potassium (SK)(More)
Voltage-gated potassium (Kv) channels control action potential repolarization, interspike membrane potential, and action potential frequency in excitable cells. It is thought that the combinatorial association between distinct alpha and beta subunits determines whether Kv channels function as non-inactivating delayed rectifiers or as rapidly inactivating(More)
To elucidate the role of thyroid hormone receptors (TRs) alpha1 and beta in the development of hearing, cochlear functions have been investigated in mice lacking TRalpha1 or TRbeta. TRs are ligand-dependent transcription factors expressed in the developing organ of Corti, and loss of TRbeta is known to impair hearing in mice and in humans. Here,(More)
Individual members of the mammalian SLC26 anion transporter family serve two fundamentally distinct functions. Whereas most members transport different anion substrates across a variety of epithelia, prestin (SLC26A5) is special, functioning as a membrane-localized motor protein that generates electrically induced motions (electromotility) in auditory(More)
Large-conductance calcium- and voltage-activated potassium channels (BKCa) are dually activated by membrane depolarization and elevation of cytosolic calcium ions (Ca2+). Under normal cellular conditions, BKCa channel activation requires Ca2+ concentrations that typically occur in close proximity to Ca2+ sources. We show that BKCa channels affinity-purified(More)
Small conductance Ca(2+)-activated K+ channels (SK channels) couple the membrane potential to fluctuations in intracellular Ca2+ concentration in many types of cells. SK channels are gated by Ca2+ ions via calmodulin that is constitutively bound to the intracellular C terminus of the channels and serves as the Ca2+ sensor. Here we show that, in addition,(More)
The defining characteristic of large-conductance Ca(2)(+)- and voltage-activated K(+) channels (BK(Ca)) is their allosteric activation by two distinct stimuli, membrane depolarization and cytosolic Ca(2)(+) ions. In this allosteric gating, increasing cytosolic Ca(2)(+) concentration ([Ca(2)(+)](i)) shifts the depolarization required for channel opening into(More)
The deafness caused by early onset hypothyroidism indicates that thyroid hormone is essential for the development of hearing. We investigated the underlying roles of the TRalpha1 and TRbeta thyroid hormone receptors in the auditory system using receptor-deficient mice. TRalpha1 and TRbeta, which act as hormone-activated transcription factors, are encoded by(More)
Cochlear inner hair cells (IHCs) transduce sound-induced vibrations into a receptor potential (RP) that controls afferent synaptic activity and, consequently, frequency and timing of action potentials in the postsynaptic auditory neurons. The RP is thought to be shaped by the two voltage-dependent K+ conductances, I(K,f) and I(K,s), that are carried by(More)
Prestin, a transporter-like protein of the SLC26A family, acts as a piezoelectric transducer that mediates the fast electromotility of outer hair cells required for cochlear amplification and auditory acuity in mammals. Non-mammalian prestin orthologues are anion transporters without piezoelectric activity. Here, we generated synthetic prestin (SynPres), a(More)