Figure 14.

Signalling pathways underlying excitation-contraction coupling. β-Adrenergic receptor (βAR) activation through stimulatory guanine nucleotide-binding (G_s) proteins increases cellular cAMP levels (A). This in turn drives a phosphokinase-A (PKA)-mediated phosphorylation and activation of L-type Ca²⁺ channels and cardiac ryanodine receptor (RyR2) SR-Ca²⁺ release channels (A) and the exchange protein directly activated by cAMP (Epac) pathway producing a calmodulin kinase II (CaMKII)-mediated RyR2 activation (B). Either action on the Ca²⁺-induced Ca²⁺ mechanism impinges on the level of SR Ca²⁺ release (C), and consequent alterations in cytosolic Ca²⁺ (D). Experimentally used agonists (+) and antagonist (−) agents used on these pathways include isoproterenol, H-89, 8-pCPT-2-O-Me-cAMP (8-CPT), and KN-93.