Figure 8.

Diagram of possible mechanisms underlying the modulation of I_Kr induced by activation of α_1A‐adrenoreceptors or AT₁ receptors via PKC isoform‐specific signalling. The activation of α_1A‐adrenoreceptors or AT₁ receptors at the plasma membrane initiates downstream signalling through the Gq proteins, leading to activation of PLC, hydrolysis of phosphatidylinositol 4,5‐bisphosphate into IP₃ and DAG (1,2‐diacylglycerol), and increases in IP₃/calcium signalling, and then mainly activate PKCα and PKCε respectively. The activated PKCα depresses I _Kr through phosphorylating T74 or a different molecule which interacts with the PAS domain or elsewhere in the N‐terminus of the channel, whereas PKCε acts through one or more of the other 17 potential phosphorylation sites.