Abstract
Activators of the slow delayed rectifier K+ current (IKs) are promising tools to suppress ventricular arrhythmias originating from prolongation of action potentials. A recently synthesized compound, L-364,373, was shown to activate IKs in ventricular cells isolated from guinea pigs and rabbits. Due to the interspecies differences known to exist in the properties of the delayed rectifier K+ currents, the effect of L-364,373 on IKs was studied and compared with that of another IKs activator mefenamic acid in canine ventricular myocytes. Mefenamic acid (100 μM) significantly increased the amplitude of the fully activated IKs current, as well as the IKs current tails, by shifting the voltage dependence of its activation towards negative voltages and increased the time constant for deactivation. In contrast, L-364,373, up to concentrations of 3 μM, failed to augment IKs at any membrane potential studied, but slightly increased the time constant of deactivation. It is concluded that human studies are required to evaluate the therapeutically beneficial effects of IKs activators. Rodent cardiac tissues are not suitable for this purpose.
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Acknowledgements
Financial support for the studies was provided by grants from the Hungarian Research Found (OTKA-T043182, OTKA-T048698), and the National Research and Development Programs (NKFP-1A/0011/2002, NKFP-1A/008/2004). The experiments comply with the current laws of Hungary.
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Magyar, J., Horváth, B., Bányász, T. et al. L-364,373 fails to activate the slow delayed rectifier K+ current in canine ventricular cardiomyocytes. Naunyn Schmied Arch Pharmacol 373, 85–90 (2006). https://doi.org/10.1007/s00210-006-0047-4
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DOI: https://doi.org/10.1007/s00210-006-0047-4