The mechanisms of propofol-induced block on ion currents in differentiated H9c2 cardiac cells

General anesthetic propofol (2,6-bis(isopropyl)-phenol) possess a chemical structure unrelated to other anesthetic drugs. It has been known to block a variety of ion currents. This study is designed to determine the effect of this drug on ion currents in differentiated H9c2 cardiac cells. The effects of propofol, an intravenous anesthetic agent with a distinct chemical structure, on ion currents of differentiated clonal cardiac (H9c2) cells were investigated in this study. Propofol (10–300 μM) suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a concentration-dependent manner with an IC50 value of 36 μM. This compound reduced activation time constant and increased current inactivation, although no voltage dependency of propofol-induced block of IK(DR) can demonstrated. Neither diazoxide, pinacidil, nor caffeic acid phenethyl ester had any effect on propofol-induced block of IK(DR). Propofol (30 μM) had no effect on erg-mediated K+ current in these cells; however, it suppressed L-type Ca2+ current (ICa,L) of cardiac and skeletal types to a similar extent. Intracellular dialysis with propofol (100 μM) had no effects on IK(DR) or ICa,L. Numerical simulations of IK(DR) based on a Markovian model reproduce the experimental results and show that propofol-induced blockade of IK(DR) is associated with an decrease in forward rate of the activation process and an increase in transitional rate into the inactivated state. Propofol can suppress IK(DR) in differentiated H9c2 cardiac cells in a concentration- and state-dependent manner. These effects can significantly contribute its action on functional activity of heart cells.