The long term goals will be to identify non-neoplastic neurologic disorders which may be based on pathologies of astrocyte-neuronal interactions. More specifically the role of astrocytes in the brain edema associated with Reye's syndrome will be studied. A variety of experiments will be proposed to test the hypothesis that """"""""Mammalian astrocytes take up sodium and swell when exposed to levels of glutamate and ammonia found in Reye's syndrome. The mechanism for this sodium influx is an astrocyte specific membrane cotransport process which is involved in the normal clearance of the putative neurotransmitter, glutamate, from the neuronal microenvironment."""""""" Secondly, using patch clamping techniques experiments are proposed to address the question """"""""Does the astrocyte depolarization by glutamate represent an electrogenic cotransport of glutamate or does it represent the opening of a glutamate gated ionic channel?"""""""" Finally the effect of blocking glutamate and sodium cotransport into astrocyte will be studied. Will the blockade of glutamate sodium cotransport result in decreased astrocyte swelling? Will the accumulation of glutamate in the synaptic space result in abnormal neuronal integration?
| Tang, C M; Presser, F; Morad, M (1988) Amiloride selectively blocks the low threshold (T) calcium channel. Science 240:213-5 |
