PHARMACOLOGY OF THE TYPE I HAIR CELL/CALYX SYNAPSE

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DESCRIPTION: Experiments described in this proposal will address the hypothesis that the membrane properties of type I Vestibular hair cells can be modulated and that one source of this modulation is through transmitter release from the apical regions of the calyx terminals which innervate type I cells. Type I hair cells, found only in amniotes, are the only hair cells 'innervated by an afferent calyx that encases the basal pole of the cell. Synaptic transmission between type I cell and its associated calyceal ending is believed to be chemically mediated. Depolarization of the type I hair cell, through deflection of the hair bundle, is assumed to increase the amount of an unidentified neurotransmitter, most likely glutamate or GABA, released from the hair cell. Although the calyx fiber is known to encode afferent information from the type I hair cell, morphological evidence suggests that the upper regions of the calyx may release neuroactive substances onto the hair cell. In addition, Vestibular efferent fibers make synaptic contact with the outer face of the calyceal membrane. Thus the type I hair cell is postulated to be a presynaptic sensory cell under local control from the calyx and also possibly under central control via action of the efferents on the calyx. Recordings from solitary type I cells indicate that the whole cell ionic currents are large and variable in magnitude. It is hypothesized that these currents may be physiologically modulated, an obvious source of modulation would be through transmitter release from the calyx. Modulation of type I hair cell conductances would alter the hair cell's response to transducer current which could confer considerable flexibility on the processing of mechanoelectrical signals by the type I hair cell. To test the hypothesis that type I currents can be modulated, experiments will be carried out on dissociated gerbil type I cells. The identity of receptors on the calyceal membrane will be established by application of putative afferent and efferent transmitters (and their antagonists and agonists) to isolated calyces in whole cell patch-clamp or to outside out patches. Recordings from type I cells in situ will establish whether ionic currents in type I cells contacted by calyces are similar to those in isolated cells and the effects of nerve simulation on type I cell responses will be assessed, to verify whether type I cell conductances are under feedback control. Results from these experiments will provide information on the synaptic physiology of mammalian type I hair cells and their calyces.