Abstract
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 (ICa), late Na+ current (INa-late), rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), inward rectifier K+ current (IK1), transient outward K+ current (Ito1), and Na+/Ca2+ exchange current (INCX) 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 IK1 and the recovery kinetics of Ito. IK1 displayed a largely four-fold larger density in canine than human myocytes, and Ito 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 IK1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.
Highlights
In order to better understand the electrophysiology and pathology of the human heart, as well as for the development of new cardioactive agents, reasonably good experimental models of human ventricular cells are needed
Due to the considerable interspecies differences discussed above, it seems reasonable to focus on canine myocytes and compare their ion currents to those recorded from undiseased human cells under identical experimental conditions, which is the action potential voltage clamp in the majority of experiments presented in this article
Ito can carry small but measurable current during the plateau and early phase 3 repolarization supporting repolarization as part of the repolarization reserve. Another implication of the EPI–ENDO differences observed in action potential configuration is the differently shaped ICa profiles in myocytes of EPI and ENDO origin recorded under action potential voltage clamp conditions
Summary
In order to better understand the electrophysiology and pathology of the human heart, as well as for the development of new cardioactive agents, reasonably good experimental models of human ventricular cells are needed. Due to the paucity of proper experimental results, the available in silico human ventricular action potential models [1,2,3,4,5] may still suffer from serious shortcomings. Since the early nineties, when the first results on successful isolation of adult human ventricular myocytes were reported [6,7,8], the cells were digested from small tissue chunks excised from the explanted recipient diseased hearts. The most important interspecies differences observed between ventricular cells of different origins (including human, canine, rabbit, guinea pig, or rat) are reviewed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
