ION CHANNEL DIVERSITY IN PRIMARY AUDITORY NEURONS

With the increased use of cochlear implants in the clinical treatment of profound sensorineural hearing loss, it has become critical to learn as much as possible about the nerve being stimulated - the primary-auditory nerve. There are two major issues that must be examined: the neurons' electrical properties and their regenerative capacity when deprived of peripheral targets. A single element that contributes to the regulation of both of these processes are transmembrane ion channels. The goal of this project is to determine how diverse groups of ion channels observed within the primary-auditory neural membrane affect signal processing and growth regulation. Preliminary studies have shown that primary-auditory neurons of a lower vertebrate, the goldfish, possess channels within the internodal membrane that are capable of rhythmically altering the membrane potential and responding to extra-synaptic modulation. Yet the functional significance of this finding is unknown and, furthermore, it has not been determined whether these specialized membrane channels are also present in mammalian primary-auditory neurons. Since these channels could alter the duration and timing of action potentials that propagate along the length of the neuron, one functional implication is that synaptically generated signals may be modified on their way into the central nervous system. Alternatively, these channel types may be transiently incorporated into primary-auditory neurons for the regulation of processes such as growth and differentiation. Patch-clamp recordings will be made from primary-auditory neurons placed in vitro to examine the elementary properties of their ion channels. The kinetics, voltage dependence and pharmacological sensitivity of these channels will be studied to better understand their regulatory effects. Intracellular recordings will be made to evaluate the contribution of specific ion channel types to neuronal activity. Other experiments will be made to categorize electrophysiological changes related to neurite regeneration or cytodifferentiation. By using a combination of approaches to study the membrane properties of primary-auditory neurons, new insights may be gained into the fundamental mechanisms that regulate cell signaling and differentiation in the peripheral auditory system.