1. Triggering the Ca entry (1) 1.Depolarisation 2.V-dpt Ca 2+ channels opening 3.Ca2+ entry 4.Ca induced Ca release by ryanodin receptor (RyR) from SR (Sarcoplasmic Reticulum) 80 mM K+, ryanodine 12-20 nm Nifedipine (DHP) caffeine

2. Triggering the Ca entry (2) 1.Agonist (NAd, Angiotensin, Histamin, Endothelin) 2.Gq coupled receptor activated 3.PLC, IP3, DAG 4.IP3 Activate IP3 receptor 5.Ca release from SR 6.DAG activates Ca channels (L type) (ROC: receptor operated channel) 7.Ca entry from external medium caffeine

3. Maintening the Ca signal 1.Ca induced Ca release (RyR) = Ca sparks 2.Refilling of SR by SR Ca ATPase (SERCA) 3.Entry of external Ca through: - V-indpt Ca channels - cationic (stretch) channels - SOC (store operated channels) : TRP6 ? 1.Ca activates myosin light chain kinase 2.Ca wave = tonic stimulation

4. Ending the Ca signal 1.Na/Ca exchange extrude the cytoplasmic Ca 2.Ca sparks directly activates Ca dpt K+ channels 3.Ca activates Ca sensitive Chloride channels 4.Hyperpolarisation iberiotoxin Dids Niflumic acid