Multidirectional effects of ouabain on automaticity of cells in sinoauricular area in mouse, guinea pig and rabbit

The effects of ouabain on the pacemaker cells of sinoauricular (SA) node in mouse, guinea pig and rabbit were studied using standard microelectrode technique and inhibitor analysis.Ouabain (10 μmol/l) slowed down the action potentials (APs) generation frequency in mouse SA cells (n=9) by 14%. The exposition of ouabain (10 μmol/l) blocked the electrical activity in SA strips of guinea pig (n=6) and rabbit (n=5) after 11±2 min. At the same time, the sarcolemma depolarization, decrease of action potentials amplitude and maximal upstroke velocity in phase 0 (dV/dtmax) as well as increase in action potentials generation frequency as a result of shortening of diastolic depolarization phase, were registered.We assumed that the observed effects of ouabain were not only the result of different isoform sensitivity of Na+/K+-ATPase, but also of higher intracellular concentration of ([Na+]i) in mice compared to guinea pigs and rabbit. Our findings suggest that the obtained differences in mechanisms of automatism generation in these animals should betaken into account when testing promising pharmacological preparations for the treatment of arrhythmias of different genesis and development of mathematical models of action potentials generation.