Cytosolic [Ca] RyR2 open probability ECC gain Ca transient contractility DADs - SCD [Ca] Time Iso CHF.

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Cytosolic [Ca] RyR2 open probability ECC gain Ca transient contractility DADs - SCD [Ca] Time Iso CHF

IP3RRyR Skel muscle++++ Smooth m.++++ Neurons+++ IP3ActivatesNone RyanodineNoneLocks open/closes Caffeine (5 mM)InhibitsActivates Ca 2+ IP3R1 - biphasic IP3R2/3 - opens biphasic RRNoneinhibits Heparininhibitsactivates

Excitation-secretion coupling Inositol 1,4,5-trisphosphate receptors

IP3 signaling

Stable transfectant Jurkat T cells do not express IP3R1 IP3R1

Activation of IP3-gated Ca 2+ channel by fyn

Bcl-2 P Bcl-2 Bcl-2 Bcl-2 Rec Growth Factor Plasma Membrane Cytoplasm PIP2 PLC-  IP3 ER Bad P Degradation Bcl-x Bad Ca 2+ IP3R Calcineurin SERCA Ca 2+ Cytosolic TF Nuclear TF Survival Nucleus Cell Death DNA Digestion M M Akt Cytoskeletal Breakdown Cytochrome C Caspases CAD Bad Survival + X ? Calcium signaling during apoptosis Calcium signaling during apoptosis

VGCC Stretch receptor CNG nAChR IP3R RyR VDAC SERCA NCE PMCA mM [Ca] 100 nM [Ca] mM [Ca] T-tubule Sarcoplasmic reticulum Endoplasmic reticulum mitochondria