Effect of milrinone analogues on intracellular calcium increase in single living H9C2 cardiac cells

The synthesis of milrinone analogues where the 4-pyridyl moiety was replaced by an ester or amide group is reported. Only amide derivatives are able to support intracellular calcium influx following chemical depolarization with 60 mM KCl in a percentage varying from 20 to 45% of differentiated H9C2 cardiomyocytes. Those cells were differentiated after chronic exposure to 10 nM retinoic acid which induces the expression of voltage-gated calcium channels. Analogues of milrinone containing an ester function did not show significant activity.

Graphical abstractNew milrinone analogues were synthesized by removing the 4-pyridyl moiety or replacing it with an ester or amide function and their ability to interfere with the [Ca2+]i level during the plasma membrane depolarization in H9C2 cardiomyocytes was tested.Figure optionsDownload full-size imageDownload as PowerPoint slide