Lecture_5-Calcium_signaling

Broken down in neurons to produce second messenger

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broken down in neurons to produce second messenger signaling molecules Downstream mediator of PI signaling was thought to be Ca2+ because the accumulation of PI was accompanied by a rise in Ca2+ We now know that a poly phosphorylated PI derivative called PI(4,5)P2 (or phosphatidylinositol4,5 bisphosphate) is the initiating step in this signaling pathway
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PLC
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Lecture 5b: Calcium In the majority of eukaryotes, describe where Ca2+ is stored/located and explain the major force acting upon Ca2+ to cause rapid increases in internal Ca2+ levels Describe the 2 major plasma membrane transport mechanisms that determine the steady-state internal Ca2+ levels and explain how they function Explain how the ER and mitochondria contribute to the regulation of internal Ca2+ Describe the 2 major sources of Ca2+ that are involved in Ca2+ signaling Explain why the ryanodine receptor is considered to be a “pure” CICR, while the IP3 receptor is not Describe the 2 major sources of Ca2+ entry from the extracellular fluid into the cell and compare how they differ in terms of their modes of activation
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Calcium is a signaling molecule • A large Ca2+ concentration gradient exists across cell membranes (70-90 mV) with Ca2+ concentrated outside the cell • Ca2+ is also stored within cells in: endoplasmic reticulum and secretory granules (1,000 to 10,000-fold higher concentration than cytoplasm); total Ca2+ in a cell reflects primarily stored Ca2+ • Rapid changes in intracellular Ca2+ (Ca2+ i ) has evolved as an important signaling molecule – Ca2+-dependent kinases/phosphatases, alterations in K+ flux, co-factor in the activation of cAMP-dependent kinases etc.
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Ca2+ signaling Ca2+ involved in signaling comes from 2 major sources: 1) External Ca2+ through ion channels (VGCC; ionotropic receptors) 2) ER via IP3 receptor and ryanodine receptors (RYRs)
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Plasma membrane Ca2+ Plasma membrane transport processes (through ion channels) determines the steady-state Ca2+ I levels PM is impermeable to Ca2+ and therefore gates the amount entering in the cell; extracellular concentrations maintained by dietary and endocrine mechanisms Two major transport mechanisms at the PM: Ca2+-ATPase pump
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broken down in neurons to produce second messenger...

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