Figure 1.

Schematic diagram of sinoatrial node mechanisms. Autonomic regulation via adenylyl cyclase-cyclic adenosine monophosphate-Protein kinase A (AC-cAMP-PKA) signaling: the internal pacemaker mechanisms are tightly coupled with cAMP/PKA signaling through the stimulation of G-protein-coupled receptors that activate (adrenergic receptors, β-AR) or inactivate (cholinergic receptors, ChR) AC as well as Ca²⁺-calmodulin activated AC. Only the main ion channels modulated in our model by AC-cAMP-PKA signaling are represented in the figure. SERCA, sarcoplasmic reticulum Ca²⁺ ATPase; PLB, phospholamban; RyR, ryanodine; PDE, phosphodiesterase; PPT, protein phosphatase; P, phosphate.