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Locating heart failure

Local levels of cAMP regulate the precise opening of the ryanodine receptor complex—which releases calcium at the start of a heartbeat. Loss or inhibition of phosphodiesterase 4D enzymatic activity leads to calcium leak, heart failure and arrhythmia.

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Figure 1: Loss of PDE4 activity increases calcium flow through the ryanodine receptor.

Katie Ris


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Molkentin, J. Locating heart failure. Nat Med 11, 1284–1285 (2005).

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