Does levosimendan act as Ca(2+) sensitizer or PDE3 inhibitor?

British journal of pharmacology

PubMedID: 24547894

Endoh M. Does levosimendan act as Ca(2+) sensitizer or PDE3 inhibitor?. Br J Pharmacol. 2014;.
Calcium ions (Ca(2+) ) play a key role in cardiac excitation-contraction coupling. Therefore cardiac contractility is crucially regulated by modulation of cardiac Ca(2+) signaling, which is classified into three processes (Blinks & Endoh, 1986). A transient increase in intracellular Ca(2+) concentration subsequent to membrane excitation (upstream mechanism) can be detected as the Ca(2+) transient by application of Ca(2+) sensitive bioluminescent protein aequorin or fluorescent dye such as indo-1or fura-2 (Endoh, 2008). Ca(2+) binding to troponin C plays a central role by triggering the activation of thin (actin, tropomyosin, troponin) and thick (myosin) filament (central mechanism). The process subsequent to Ca(2+) binding to troponin C leading to thin and thick filament interaction (downstream mechanism) is not easy to experimentally differentiate from the central mechanism in intact myocardial cells (Endoh, 1998; 2002; 2008).