Lecture_5-Calcium_signaling

Common and ubiquitous in eukaryotic cells enables

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• Common and ubiquitous in eukaryotic cells • Enables efflux of Ca2+ against its concentration gradient • Found at both PM and ER (but different genes encode the 2 subcellularly distinct pumps) • ER: SERCA pump (sarcoendoplasmic reticulum Ca2+-ATPase-dependent pump; has its own antagonists etc. • PM: pump is controlled, in part, by Ca2+-calmodulin (thus, turned on by rapid increases in Ca2+ i ) Na+-Ca2+ exchanger • Found only in excitable cells like neurons and muscle • Drives Ca2+ out of cell, takes Na+ in along its concentration gradient • Argued that the function contributes moreso to clearing high Ca2+ following activation, rather than at rest • May work in reverse to bring in Ca2+ under conditions of low Ca2+ I
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Ca2+ storage in organelles ER is the major Ca2+ storing, buffering and signaling organelle – The lumen is full of Ca2+-binding proteins (calreticulin in most cells; calsequestrin in muscle) – ER pumps provide a rapid means of elevating Ca2+ I , sometimes coupled to Ca2+ entry at the plasma membrane (capacitative Ca2+ entry) – Ca2+ binding provides a chaperone functional that is essential for protein synthesis (i.e. synthetic enzymes require Ca2+ to make/modify new protein) Mitochondria employ an electrogenic Ca2+ channel to store Ca2+ – Energy is derived from the membrane potential across the mitochondrial membrane,which reflects H+ gradients in the electron transport chain – Drugs that interfere with mitochondrial H+ pumps or the electron transport chain will prevent Ca2+ uptake – Mitochondrial uptake has lower potency than that for the ER BUT the capacity to store is great (protects the cell against too high Ca2+ i ) – Because the ion exchange is neutral (2 H+ or 2 Na+ for 1 Ca2+), the kinetics are slower than PM or ER systems – Not a source of signaling Ca2+ Nucleus and secretory granules – Ca2+ stored in secretory granules can be released during times of cell stimulation and may control secretion – Pores in the nuclear membrane prevent the development of Ca2+ gradients between the nucleoplasm and cytoplasm; but can also sequester Ca2+ as an extension of the ER and released Ca2+ into the nucleoplasm may regulate nucleus function
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Ca2+ signaling sources
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Common and ubiquitous in eukaryotic cells Enables efflux of...

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