Milrinone enhances SERCA activity in cardiac myocytes, leading to improved relaxation.

Milrinone enhances SERCA activity in cardiac myocytes, leading to improved relaxation.

• A. True
• B. False
• C. It only enhances SERCA activity in vascular smooth muscle
• D. It decreases SERCA activity

Answer: (A)

Milrinone, a PDE-3 inhibitor, raises cAMP in cardiac myocytes. The higher cAMP activates PKA, which phosphorylates phospholamban. When phospholamban is phosphorylated, it no longer inhibits SERCA2a, so SERCA works more effectively to pump calcium back into the sarcoplasmic reticulum. Faster calcium reuptake shortens the calcium transient and speeds relaxation, improving lusitropy. This mechanism explains why milrinone can enhance relaxation in the heart. It’s also true that milrinone causes vasodilation via the same cAMP rise in vascular smooth muscle, but the SERCA-related relaxation effect is specific to cardiac myocytes. It does not decrease SERCA activity.

Milrinone, a PDE-3 inhibitor, raises cAMP in cardiac myocytes. The higher cAMP activates PKA, which phosphorylates phospholamban. When phospholamban is phosphorylated, it no longer inhibits SERCA2a, so SERCA works more effectively to pump calcium back into the sarcoplasmic reticulum. Faster calcium reuptake shortens the calcium transient and speeds relaxation, improving lusitropy. This mechanism explains why milrinone can enhance relaxation in the heart. It’s also true that milrinone causes vasodilation via the same cAMP rise in vascular smooth muscle, but the SERCA-related relaxation effect is specific to cardiac myocytes. It does not decrease SERCA activity.