Expression of Ion Channels in the Auditory System

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DESCRIPTION: The firing patterns of neurons in central auditory pathways encode specific features of sound stimuli, such as frequency, intensity and localization in space. The generation of the appropriate pattern depends, to a major extent, on the properties of the voltage-dependent potassium channels in these neurons. The Shaw-family Kv3.1 and Kv3.3 channels and the two-pore family rTWIK channel are expressed at high levels in neurons that are capable to firing at very rapid rates and that lock their action potentials to specific phases of auditory stimuli. We plan to determine the mechanisms that regulate these channels in the presynaptic terminals of cochlear nucleus neurons and their postsynaptic targets, neurons of the medial nucleus of the trapezoid body. To test the roles of these channels in timing and regulation of transmitter release, we shall record the responses of neuronal terminals and somata in which the genes for these channels have been eliminated by homologous recombination. We shall test the hypothesis that phosphorylation of the channel proteins alters the transmission of information through this synaptic pathway. Using transgenic animals in which the promoters for the channels are coupled to a fluorescent reporter gene, we shall test whether the naturally occurring differences in the level of expression of the Kv3.l channel along tonotopic axes can be induced by changes in the pattern of activity to which the neurons are exposed. An understanding of how ion channels are regulated in central auditory neurons is likely to lead to therapies for certain forms of deafness, as well as for tinnitus, disorders in the interpretation of auditory stimuli, and states of hyperexcitability such as audiogenic seizures.