The major aim of my research is to understand the process of synaptic communication at a molecular cellular level and the way that it can be modulated by neurotransmitters and drugs. In particular I have been studying the mechanisms by which Ca2+ can enter nerve cells (calcium channels), factors that regulate the [Ca2+]i in neurons and the modulation of such processes by neurotransmitters. I am also particularly interested in the mechanism of action of opioid drugs which seem to inhibit neurotransmitter release in many instances by effects on neuronal Ca2+ channels. In this proposal I suggest further studies in several areas related to Ca2+ mediated processes in neurons. These include (a) the regulation of neuronal Ca2+ channels by receptors and G-proteins. (b) The regulation of neuronal K+ channels by receptors and G-proteins. (c) The regulation of synaptic transmission by receptors and G-proteins. (d) The regulation of neuronal [Ca2+]i under different circumstances in peripheral and central neurons. (e) The regulation of neuronal [Ca2+]i by excitatory amino acids, particularly the regulation of Ca2+ mobilization from intracellular stores and its role in synaptic transmission. (f) The regulation of [Ca2+]i in astrocytes by neurotransmitters. (g) The regulation of [Ca2+]i in identified anterior pituitary cells by hypothalamic factors and its role in the control of hormone secretion and (h) The construction of equipment for performing combined electrophysiology (patch-clamp) and [Ca2+]i measurements in thin slices from brain.
