Positive Inotropic Effects of Levosimendan are Modulated by KATP Channels in Isolated Human Atrial Trabeculae

Objective: The aim of this study was to investigate whether potassium channel blocking agents were able to modulate positive inotropic effect of levosimendan in isolated human atrial trabecular muscles or not. Material and Methods: The right atrial appendage samples (1 cm2, 500-1000 mg) were removed and immersed in preoxygenated and modified Tyrodes solution. Preparations were used to investigate the concentration-effect relation of levosimendan (10-9 to 10-4 M) alone or in the presence of Ca2+-dependent potassium channel blocker 4-aminopyridine (4-AP: 500 ?M), ATP-dependent potassium channel blocker glibenclamide (1 ?M) or mitochondrial ATP-dependent potassium channel blocker 5-hydroxydecanoate (5-HD: 300 ?M) on percent developed tension (%DT). Results: Levosimendan produced concentration-dependent increments in %DT. Both the sensitivity (pD2) and maximum response (Emax) of human atrial trabeculae to levosimendan (7.31 ± 0.02 and 29.2 ± 1.1 mN, respectively) significantly and similarly reduced in presence of glibenclamide (5.83 ± 0.04 and 17.4 ± 1.61 mN) and 5-HD (6.14 ± 0.05 and 18.5 ± 3.1 mN). However, 4-AP did not cause a significant alteration in sensitivity (pD2= 6.77 ± 0.05) or Emax (27.6 ± 2.0 mN) to levosimendan. Conclusion: Both sarcolemmal and mitochondrial ATP-dependent potassium channels are implicated to modulate positive inotropic effect of levosimendan in human atrial trabeculae.