Late sodium current in human, canine and guinea pig ventricular myocardium
| Autor: | Kornél Kistamás, Balázs Horváth, Richárd S. Varga, D Baranyai, Norbert Nagy, András Varró, Tamás Bányász, Péter Gazdag, Roland Veress, Tamás Hézső, Norbert Szentandrássy, János Almássy, Csaba Dienes, Tamás Árpádffy-Lovas, János Magyar, Péter P. Nánási, László Virág, István Baczkó |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Voltage clamp Heart Ventricles Guinea Pigs Action Potentials Tetrodotoxin 030204 cardiovascular system & hematology Calcium in biology Sodium Channels Sodium current Ventricular myocardium Guinea pig 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cnidarian Venoms Dogs Myocyte Animals Humans Myocytes Cardiac Molecular Biology Myocardium Cardiac action potential 030104 developmental biology chemistry Biophysics Cardiology and Cardiovascular Medicine Ion Channel Gating |
| Zdroj: | Journal of molecular and cellular cardiology. 139 |
| ISSN: | 1095-8584 |
| Popis: | Although late sodium current (INa-late) has long been known to contribute to plateau formation of mammalian cardiac action potentials, lately it was considered as possible target for antiarrhythmic drugs. However, many aspects of this current are still poorly understood. The present work was designed to study the true profile of INa-late in canine and guinea pig ventricular cells and compare them to INa-late recorded in undiseased human hearts. INa-late was defined as a tetrodotoxin-sensitive current, recorded under action potential voltage clamp conditions using either canonic- or self-action potentials as command signals. Under action potential voltage clamp conditions the amplitude of canine and human INa-late monotonically decreased during the plateau (decrescendo-profile), in contrast to guinea pig, where its amplitude increased during the plateau (crescendo profile). The decrescendo-profile of canine INa-late could not be converted to a crescendo-morphology by application of ramp-like command voltages or command action potentials recorded from guinea pig cells. Conventional voltage clamp experiments revealed that the crescendo INa-late profile in guinea pig was due to the slower decay of INa-late in this species. When action potentials were recorded from multicellular ventricular preparations with sharp microelectrode, action potentials were shortened by tetrodotoxin, which effect was the largest in human, while smaller in canine, and the smallest in guinea pig preparations. It is concluded that important interspecies differences exist in the behavior of INa-late. At present canine myocytes seem to represent the best model of human ventricular cells regarding the properties of INa-late. These results should be taken into account when pharmacological studies with INa-late are interpreted and extrapolated to human. Accordingly, canine ventricular tissues or myocytes are suggested for pharmacological studies with INa-late inhibitors or modifiers. Incorporation of present data to human action potential models may yield a better understanding of the role of INa-late in action potential morphology, arrhythmogenesis, and intracellular calcium dynamics. |
| Databáze: | OpenAIRE |
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