Over one hundred neurotransmitters and hormones, acting on their respective receptors and receptor-channels, relay their signals by altering intracellular calcium concentration. For the generation of calcium signals, cells depend on the large electrochemical gradient of calcium across the plasma membrane, or across the endoplasmic reticulum membrane. There are several pathways controlling calcium influx, including ligand-gated receptor-channels and voltage-gated calcium channels. Calcium release from endoplasmic reticulum is activated by G protein-coupled and tyrosine kinase receptors, and is mediated through inositol (1,4,5)-trisphosphate)-sensitive receptor-channels. Many excitable cells also express ryanodine-sensitive calcium release channels in their endoplasmic/sarcoplasmic reticulum, and these are coupled to voltage-gated calcium channels by a mechanism termed calcium-induced calcium release.
The main objectives of current investigations in the Section on Cellular Signaling are to clarify the mechanisms that control calcium signaling and to elucidate the role of calcium ions as intracellular messenger in neuroendocrine and endocrine cells. The approach in the laboratory has been to characterize calcium signaling in these cells from biophysical, physiological, and pharmacological points of view. More recently, we have begun to use molecular biological approaches to identify molecules participating in the generation and control of calcium signals, as well as to address the issues of how the calcium signaling function in these cells is related to the structure of individual receptors and channels. Current research includes studies on the receptor- and intracellular messenger-mediated control of voltage-gated calcium influx; the structure and function of purinergic receptor-channels; cyclic nucleotide-controlled membrane excitability and calcium signaling; the role of calcium in controlling plasma membrane and endoplasmic reticulum excitability; the dependence of cyclic nucleotide production on calcium; and the relevance of the pattern of calcium signaling to cell-type specific hormone secretion patterns.
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