Effects of trimetazidine on action potentials and membrane currents of guinea-pig ventricular myocytes.
The effects of trimetazidine on membrane potentials and membrane currents of enzymatically isolated guinea-pig ventricular cells were studied with the use of giga-seal suction pipettes for patch clamp. Trimetazidine (3 X 10(-5) M) decreased the action potential duration from 433 +/- 179 ms (mean and S.D., n = 9) to 319 +/- 156 ms within 8 mins. In voltage clamp experiment, trimetazidine at a concentration of 1.5 X 10(-4) M decreased the peak amplitude of calcium current by 40% (0.92 +/- 0.46 nA to 0.55 +/- 0.19 nA, mean +/- S.D., n = 5). The effect on calcium current was rate-dependent, e.g., at 1 Hz, trimetazidine blocked a larger fraction of the calcium current than at 0.2 Hz. The drug decreased the conductance of potassium current which flows via inward rectifier potassium channel from 28 +/- 11 nS to 19 +/- 10 nS, n = 5, P less than 0.05). Trimetazidine shifted the steady state current-voltage relationship outward at potentials positive to -20 mV. This shift was not due to the enhanced time- and voltage-dependent outward current (Ik). From these findings, it was concluded that trimetazidine shortens action potential duration by blocking the calcium channels with increases in steady state outward current or a possible blockade of non-inactivated component of the calcium current, at the plateau potentials. The reduction of calcium current and of inward rectifier potassium current may protect the cardiac cells from accumulation of calcium ions and from loss of potassium ions, in the presence of ischemia.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D014292:Trimetazidine / Q000494:pharmacology*; D016276:Ventricular Function
D007473:Ion Channels; D010879:Piperazines; D014292:Trimetazidine; D002118:Calcium