FIGURE 11.

Schematic illustration of signal transduction via β-adrenoceptors in cardiomyocytes and the role of PPs. β-adrenoceptor (β-AR) stimulation by isoproterenol leads via stimulatory G-proteins (G_s) to increased activity of adenylyl cyclase (AC) which increases cAMP in the cytosol and activation of a cAMP-dependent protein kinase (PKA). This kinase can phosphorylate (P) many cardiac proteins: here phosphorylation of the L-type Ca²⁺channels (LTCC) with subsequent increase of Ca²⁺ flow through the sarcolemma, phosphorylation of the ryanodine receptor 2 (RYR) of the junctional sarcoplasmic reticulum or phosphorylation of phospholamban (PLB) which increases the activity of the sarcoplasmic reticulum Ca²⁺ ATPase (SERCA) and thereby Ca²⁺ uptake into the sarcoplasmic reticulum where Ca²⁺ is stored by calsequestrin (CSQ). Moreover, phosphorylation of the troponin inhibitor (TnI) is indicated which enhances relaxation of the heart. These phosphorylations can be reversed by PP2A and/or PP2C.