title: Molecular organization of a type of peripheral glutamate synapse: the afferent synapses of hair cells in the inner ear.
abstract: The synapses between sensory cells in the inner ear and the afferent dendrites of ganglion cells are well suited to investigations of fundamental mechanisms of fast synaptic signalling. The presynaptic elements can be isolated for electrophysiological and functional studies while the synapses can be easily recognized in the electron microscope due to their distinct morphological features. This allows for a broader range of correlative functional and structural analyses than can be applied to synapses in the central nervous system (CNS). As in most fast excitatory synapses in the CNS the transmitter in the afferent hair cell synapses appears to be glutamate or a closely related compound. Recent studies have revealed many of the key molecular players at this type of synapse and how they are spatially and functionally coupled. By use of high resolution immunogold cytochemistry it has been shown that AMPA glutamate receptors are specifically expressed in the postsynaptic specialization of afferent hair cell synapses (except at those established by outer hair cells in the organ of Corti) and that their density varies as a function of the distance from the release sites (demonstrated for the afferent contacts of inner hair cells). The glutamate transporter GLAST is localized in supporting cell membranes and concentrated in those membrane domains that face the synaptic regions. Glutamine synthetase and phosphate-activated glutaminase--which are responsible for the interconversion of glutamate and glutamine--are selectively localized in non-neuronal and neuronal elements, respectively. Taken together with quantitative immunogold data on the cellular compartmentation of glutamate and glutamine the above findings suggest that the sensory epithelia in the inner ear sustain a cycling of glutamate carbon skeletons. In this process, the supporting cells may carry out functions analogous to those of glial cells in the CNS. Functional and morphological analyses of the presynaptic membrane indicate that L-type Ca(2+)-channels and Ca(2+)-activated K(+)-channels are colocalized and clustered at the active zone. Influx through the L-type channels triggers synaptic release and their close spatial association with Ca(2+)-activated K(+)-channels appears to be critical for frequency tuning. The focal expression of different Ca(2+)-channels combined with a high intracellular buffering capacity permits several Ca(2+)-signalling pathways to operate in parallel without undue interference. The molecular organization of the afferent hair cell synapses reflects the functional demand for speed and precision and attests to the ability of the pre- and postsynaptic elements to target and anchor key proteins at specific membrane domains.
authors.affiliation: Department of Anatomy, Institute of Basic Medical Sciences, Oslo, Norway.
authors.forename: O P
authors.initials: OP
authors.lastname: Ottersen
authors.forename: Y
authors.initials: Y
authors.lastname: Takumi
authors.forename: A
authors.initials: A
authors.lastname: Matsubara
authors.forename: A S
authors.initials: AS
authors.lastname: Landsend
authors.forename: J H
authors.initials: JH
authors.lastname: Laake
authors.forename: S
authors.initials: S
authors.lastname: Usami
mesh_terms: D000818:Animals; D018698:Glutamic Acid / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000737:chemistry* / Q000648:ultrastructure*; D006801:Humans; D017470:Receptors, Glutamate / Q000032:analysis / Q000502:physiology; D013569:Synapses / Q000737:chemistry* / Q000502:physiology*
chemical_list: D017470:Receptors, Glutamate; D018698:Glutamic Acid