Potassium currents that contribute to the repolarization of the cardiac action potential show major differences among species with respect to both their presence and their relative importance. For instance, Ito is absent in guinea pig myocytes, which are repolarized by two components of the delayed rectifier IKr and IKs , whereas in rat ventricular myocytes Ito is the main repolarizing current . Therefore, it is of great importance also to investigate the effects on potassium currents of human cardiac cells of potassium channel blocking agents that are intended for use as antiarrhythmic cheap drugs. The effects of the class III antiar-rhythmic agent tedisamil on three potassium currents found in the human heart (ie, Ito in human ventricular subepicardial myocytes ; Ito of human atrial myocytes; and noninactivating Iso, which is present only in atrial cells) were investigated.
Tedisamil acted on these outward currents as an open channel blocker: the reduction of the current amplitude was use-dependent and it recovered completely from block at negative membrane potentials where transition of channels towards a closed state are favoured. Effects of tedisamil on Ito in human atrial and ventricular myocytes were slightly different; in particular, the inactivation time course was more affected in ventricular cells. In atrial myocytes, tedisamil was similarly effective with respect to reduction of Iso and Ito amplitude, and the IC50 values were of the same order of magnitude. Because Iso is hardly inactivated at all under control conditions, the influence of tedisamil on Iso affects the atrial action potential to a greater extent than its influence on Ito. Get most advantageous deals offered to you by the pharmacy you are going to appreciate soon after you become its customer: you now can get your nolvadex price any time of the day or night with very fast delivery and quality guarantees.