We shall utilize fura-2 based microspectrofluorimetry and imaging techniques to investigate the regulation of (Ca2+)i in vertebrate neurons from the central and peripheral nervous systems. In the first series of studies we shall investigate the properties of intracellular bound stores of Ca2+ within neurons. We shall ascertain the distribution of these stores and whether they can be regulated by methylxanthines such as caffeine or by inositol trisphosphate (IP3). Furthermore, we shall investigate the effect of various neurotransmitters on phospholipid metabolism in different types of central and peripheral neurons in vitro. Secondly, we shall also continue to investigate the different types of voltage sensitive Ca2+ channels found in vertebrate neurons. In particular we shall investigate the distribution of different types of Ca2+ channels in single neurons in vitro. We shall also continue to investigate the mechanism by which neuronal Ca2+ currents can be regulated by neurotransmitters and whether this modulation occurs in different parts of the neuron. We shall continue to analyze the molecular basis for Ca2+ current modulation in neurons and in particular the role of G-proteins and protein kinase C in this process. We shall also continue to investigate receptor operated Ca2+ channels in neurons, particularly those activated by the excitatory amino acid glutamate. We shall continue to characterize the ionic channels linked to these receptors and the way that they can be modulated by low concentrations of glycine. Finally, we shall attempt to measure changes in (Ca2+)i in neurons in slice preparations from the central nervous system. In such a situation the cells will be in a more """"""""normal"""""""" environment. We hope to be able to characterize changes in (Ca2+)i occurring in CA1 pyramidal cells during the induction of long term potentiation and to assess whether such changes are sine quae non for the establishment of this phenomenon.
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