The Effects Of Glutamate On The Cochlear IHCs And GLAST And The Hearing Threshold

The glutamate is the important stimulant medium related to synaptic transmission between the cochlear IHCs and the primary neuron. Recently, people proposed the concept of glutamate excitotoxicity corresponding to the cells damage following the excessive release of EAA due to the lack of blood and oxygen . Namely it refers to a series of activities of postsynaptic neuron as a consequence of overactivation of EAA receptor, esp. glutamate receptor, until cells death.The excited amino acid(EAA) is neurotoxic, which can selectively damage the neuron excited by it. Some scholars think the final result of acute and chronic pathological changes is that glutamate receptors are to be overexcited. Therefore, the research and development of effective glutamate receptor anagonism for clinical usage will be a revolution on the neuron science. The researches suggest that glutamate is the primary neurotransmitter between IHCs and primary auditory afferent neurons . The role of glutamate and its receptors in different kinds of cochlea diseases is becoming a focus in the earneuron science. Many researches also show that the blood and oxygen lacking in the cochlea or/and the excessive noise stimulation can cause the IHCs and supporting cells to release massive glutamate that harms the cochlea primarily. The blockage of glutamate release or functioning of glutamate receptor activated by it can lightened the glutamate excitotoxicity.Glutamate is the primary neural medium between IHCs and primary auditory afferent neurons. Activations of receptors of L-transpyrrolidine-2 and 4-dicarboxylic acid (AMPA) make the fast transmission of the feeling. However, the persistent high concentration of extracellular glutamate is cellulotoxic, which has to be controlled to avoid the damage to the neural afferent endings.The experiment suggests that the glutamate released to the synaptic cleft by the neural endings is not deactivated by enzymolysis, but mainly re-taken up by high affinity GLAST in the neural endings and in the glial membrane to terminate its synaptic transmission. Eybalin proposed the Glu-Gln recurrence mechanism and suggested the supporting cells adjacent to IHCs in the cochlea is the area taking up the redundant glutamate in the synaptic cleft.Optics and the electron microscope immunocytochemistry research suggests that GLAST occurs in the IHCs' supporting cells and in the spiral ganglion satellite cells in the cochlea of mouse and guineapig. GLAST formed a powerful uptake system which can rapidly take up extracellular glutamate.GLAST takes up type L glutamate with the Km value of 77 uM. In the static condition, extracellular glutamate density is about 1 uM. In the excitatory synaptic transmission, the uptake of transporter enhances. In the pathological state, for example, blood lacking in brainor oxygen lacking, extracellular glutamate concentration rises and then has been neurotoxic. GLAST is activated in pathology condition, involving uptake of extracellular glutamate, thus accelerates the elimination of the extracellular glutamate concentration to prevent the neural cell from further damage.David N. Furness, through synaptic ultrastructure researches of guinea pig OHCs and postembedding immunogold labelling, explained that, the distribution of GLAST around OHCs within the cochlea is consistent with two roles: (1) its involvement in a localized synaptic glutamate uptake mechanism associated with the OHC afferents, perhaps contributing to shaping the as yet uncharacterized activity at these synapses, and (2) participation in a more widespread cochlear uptake requirement arising from mechanical dispersal of glutamate throughout the perilymphatic compartment that protects the neuronal elements from excitotoxicity. And more GLAST is required according to the release of more glutamate.This experiment supplies extraneous glutamate by surgery in order to make sure how the extraneous glutamate influences the inner ear hair cell and the hearing threshold. In the surgery, artificial damage is to be reduced as far as possi...