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. Author manuscript; available in PMC: 2014 Sep 5.
Published in final edited form as: Nat Rev Drug Discov. 2014 Apr;13(4):290–314. doi: 10.1038/nrd4228

Figure 3. PDE-containing signalosomes couple cAMP–PKA signalling to myocardial contractility.

Figure 3

Phosphodiesterase 4B (PDE4B), as a component of an A-kinase anchor protein 15/18 (AKAP15/AKAP18α)-based signalosome in the cardiac L-type calcium channel (LTCC) complex, regulates the calcium current and protects against ventricular arrythmias in mice167. AKAP6 (also known as mAKAP) serves as a scaffold for a PDE4D3-containing signalosome that is involved in regulating the release of calcium from the sarcoplasmic reticulum via the ryanodine receptor channel168. PDE3A, as a component of a sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) AKAP18δ-containing signalosome, is an important regulator of the effects of cAMP on calcium uptake into the sarcoplasmic reticulum169. NCX, sodium/calcium exchanger; PKA, protein kinase A; PKA-C, PKA catalytic domain; PKA-R, PKA regulatory domain; PLB, phospholamban; PMCA, plasma membrane calcium-transporting ATPase; PP2A, protein phosphatase 2A; Rg, PP2A regulatory subunit; TNNC, troponin C; TNNI, troponin I.