The primary objective of the proposed study is to characterize the voltage-dependent conductances of hippocampal neurons and examine their modulation by neurotransmitters and pharmacological agents. The specific objectives are (1) To examine the properties and Ca++ dependency of three voltage- dependent K+ currents in the hippocampal cells. (2) To further characterize the calcium current; to examine its selectivity, kinetic and pharmacological properties and to use this information to assess the number of different Ca channel types that may be involved in its generation. (3) To determine the site and mode of action of two neurotransmitters, acetylocholine and norepinephrine, on the Ca and K channels. These transmitters are known to be involved in modulating the epileptiform activities of cortical neurons. Experiments will be carried out on acutely dissociation cells from hippocampus of adult guinea pigs. We have develped the dissociation technique and finalized the procedure so that viable neurons can be consistently obtained. Our results show that the cells have clean membrane surfaces allowing the application of patch-clamp technique for whole-cell and single channel recordings. Our previous data have made clear the role of single hippocampal pyramidal cells in the generation of epileptiform activities. Specifically we observed that burst firing in a single pyramidal cell can initate and entrain epileptiform synchrony in the hippocampal slice. The proposed studies on excitability of hippocampal neurons and its regulation by transmitters will be relevant to our understanding of the initiation and control of epileptiform activities in the cortex.
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