The proposed studies address the chemical mechanism of the excitatory serotonin type-3 receptor as expressed in NIE-115 cells. Two rapid kinetic approaches will be employed: (1) a cell-flow method, and (2) laser-pulse photolysis of labile serotonin cage species. Transmembrane channel behavior will be investigated over wide ranges of time and serotonin concentration. The effects of inhibitors will be explored. %%% Neurotransmitter receptor-mediated reactions in specific cells of the nervous system account for the initiation, regulation, and modulation of signal transmission. These processes are all required for nervous system function. The studies proposed are aimed at developing a complete kinetic understanding of the interaction between a ligand (serotonin) and its receptor in selected cell membranes. Depending on whether serotonin is bound to the receptor and for how long, the receptor forms transient ion- conducting transmembrane channels which provide the fundamental signal transmission event. Careful time-dependence studies are required in order to develop useful models of signal transmission. Development of such basic information is fundamental to progress in understanding the nature of nervous system function and integration.
