Canine Myocytes Represent a Good Model for Human Ventricular Cells Regarding Their Electrophysiological Properties

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca²⁺ current (I_Ca), late Na⁺ current (I_Na-late), rapid and slow components of the delayed rectifier K⁺ current (I_Kr and I_Ks, respectively), inward rectifier K⁺ current (I_K1), transient outward K⁺ current (I_to1), and Na⁺/Ca²⁺ exchange current (I_NCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of I_K1 and the recovery kinetics of I_to. I_K1 displayed a largely four-fold larger density in canine than human myocytes, and I_to recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger I_K1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.