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Observation: CICR in A7r5 not IP3R or RyR no Passive exchange 2. Characteristics of CICR

Observation: CICR in A7r5 not IP3R or RyR no Passive exchange 2. Characteristics of CICR Ca2+ dependence overlapping stores blocked by MgCl2 ATP dependent 3. Regulation CaM has no effect Inhibition by CaM1234, NCS-1, NCS-1 E120Q, sCaBP1, lCaBP1

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Observation: CICR in A7r5 not IP3R or RyR no Passive exchange 2. Characteristics of CICR

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  1. Observation: CICR in A7r5 • not IP3R or RyR • no Passive exchange • 2. Characteristics of CICR • Ca2+ dependence • overlapping stores • blocked by MgCl2 • ATP dependent • 3. Regulation • CaM has no effect • Inhibition by CaM1234, NCS-1, NCS-1 E120Q, sCaBP1, lCaBP1 • model: release of apoCaM from the IP3R by Ca2+ activates CICR (experiments with peptides !)

  2. Fig. 1

  3. No passive exchange Fig. 2b Fig. 2a

  4. Fig. 3 IP3R en RyR inhibitoren

  5. Fig. 4 Ca2+ Dependence

  6. Fig 5 Mg2+ Dependence ATP dependence

  7. Fig. 6a Fig. 6b

  8. Calcium-binding proteins Calmodulin Calmodulin1234 Long CaBP1 Short CaBP1 NCS-1/Frequenin

  9. Fig. 8

  10. Calcium-binding proteins Calmodulin Calmodulin1234 Long CaBP1 Short CaBP1 NCS-1/Frequenin

  11. NCS-1/Frequenin E120Q NCS-1/Frequenin Frequenin: neuronal calcium-sensor1 • Regulatory role in synaptic neurotransmission • Regulatory role in steps leading to Ca2+-dependent exocytosis of synaptic vesicles and dense core granules in neurons an neuroendocrine cells • Activation of various calmodulin targets: phosphodiesterase, calcineurin, nitric-oxide synthase • Role in direct or indirect activation of Ca2+ -dependent K+ channels and Na2+ /Ca2+ exchange • Ca2+-dependent conformational change, Ca2+ -independent interaction with membranes

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