Fig. 5.

Proposed mode of action of ANG II via activation of intracellular AT₁ receptors. Intracellular ANG II transferred into the endo-lysosomes (Lys) via microautophagy acts on AT₁ receptors situated on acid-filled Ca²⁺ stores and activates lysosomal PLC followed by production of IP₃ from phosphatidylinositol 4,5-bisphosphate (PIP₂). IP₃ activates IP₃R on ER, increasing [Ca²⁺]_i. The increase in [Ca²⁺]_i may activate ryanodine receptors (RyR) and further potentiates Ca²⁺ release from the ER via a Ca²⁺-induced Ca²⁺ release (CICR) mechanism.