Observation: CICR in A7r5 not IP 3 R or RyR no Passive exchange 2. Characteristics of CICR

1. Observation: CICR in A7r5 • not IP3R or RyR • no Passive exchange • 2. Characteristics of CICR • Ca2+ dependence • 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. 2

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 Calmodulin1 Calmodulin1234 Long CaBP1 Short CaBP1 NCS-1/Frequenin NCS-1/FrequeninE120Q

9. Fig. 8

10. 45 min Load Efflux Load Load + CaM-binding peptide Ca 2+