The long term goal of this work is to understand the mechanisms that generate neuronal activity, and modulation of that activity by neurotransmitters. The first step is characterization of the voltage- dependent ion channels of frog sympathetic neurons, using whole-cell and single channel patch clamp techniques. These cells are particularly favorable for voltage clamp studies, and much is already known about the channels underlying electrical activity in sympathetic neurons. A major part of the project will involve study of the voltage-dependent calcium channels, and comparison of those channels to calcium channels in other cell types. Kinetic models of the behavior of calcium and other channels will be developed, to construct a computer model of electrical activity in these cells. The model will be tested by comparing action potentials, and patterns of action potentials, generated by the model to those actually produced by sympathetic neurons. This analysis of the normal behavior of the cell will be supplemented by study of the effects of neurotransmitters on the preexisting voltage-dependent currents. One goal is to explain quantitatively the increased excitability of frog sympathetic neurons induced by slow synaptic potentials.
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