Cholinergic Inhibition of Hair Cells in the Inner Ear

KATZ E; ELGOYHEN AB; FUCHS PA

Auditory and Vestibular Efferents

Springer

Año: 2011; p. 103 - 133

In the inner ear, the activity of hair cells that transform sound into electrical signals is modulated by a descending efferent innervation from the brain. A major component of this feedback involves cholinergic inhibition of hair cells via an unusual ionic mechanism. It activates rapidly (on the order of milliseconds), but instead of being mediated by a hyperpolarizing conductance through g-aminobutyric acid (GABA) and/or glycine receptors, it is served by nicotinic cholinergic receptors (nAChR), which usually mediate excitatory postsynaptic responses. How is fast inhibition accomplished if the activation of a cationic channel (the nAChR) at the resting membrane potential should depolarize the hair cell? Current data show that this response occurs via the activation of a peculiar type of nAChR that allows calcium entry into the hair cell with the subsequent activation of calcium-activated potassium channels that hyperpolarize the cell membrane. This chapter focuses on the experimental evidence that gives support to this “twochannel hypothesis”: electrophysiological experiments performed on hair cells from lower vertebrates, cloning and cellular localization of the nAChR subunits that make up the hair cell receptor, and electrophysiological recordings from inner and outer hair cells in a microdissected preparation of the mammalian organ of Corti. Finally, the focus will turn to the generation and analysis of mouse models with genetic modifications of the molecules that are key participants in this peculiar type of fast synaptic inhibition. cholinergic receptors (nAChR), which usually mediate excitatory postsynaptic responses. How is fast inhibition accomplished if the activation of a cationic channel (the nAChR) at the resting membrane potential should depolarize the hair cell? Current data show that this response occurs via the activation of a peculiar type of nAChR that allows calcium entry into the hair cell with the subsequent activation of calcium-activated potassium channels that hyperpolarize the cell membrane. This chapter focuses on the experimental evidence that gives support to this “twochannel hypothesis”: electrophysiological experiments performed on hair cells from lower vertebrates, cloning and cellular localization of the nAChR subunits that make up the hair cell receptor, and electrophysiological recordings from inner and outer hair cells in a microdissected preparation of the mammalian organ of Corti. Finally, the focus will turn to the generation and analysis of mouse models with genetic modifications of the molecules that are key participants in this peculiar type of fast synaptic inhibition. -aminobutyric acid (GABA) and/or glycine receptors, it is served by nicotinic cholinergic receptors (nAChR), which usually mediate excitatory postsynaptic responses. How is fast inhibition accomplished if the activation of a cationic channel (the nAChR) at the resting membrane potential should depolarize the hair cell? Current data show that this response occurs via the activation of a peculiar type of nAChR that allows calcium entry into the hair cell with the subsequent activation of calcium-activated potassium channels that hyperpolarize the cell membrane. This chapter focuses on the experimental evidence that gives support to this “twochannel hypothesis”: electrophysiological experiments performed on hair cells from lower vertebrates, cloning and cellular localization of the nAChR subunits that make up the hair cell receptor, and electrophysiological recordings from inner and outer hair cells in a microdissected preparation of the mammalian organ of Corti. Finally, the focus will turn to the generation and analysis of mouse models with genetic modifications of the molecules that are key participants in this peculiar type of fast synaptic inhibition.