scholarly journals Separation of the components of the delayed rectifier potassium current using selective blockers of IKr and IKs in guinea-pig isolated ventricular myocytes

1996 ◽  
Vol 81 (4) ◽  
pp. 587-603 ◽  
Author(s):  
BM Heath ◽  
DA Terrar
1999 ◽  
Vol 90 (1) ◽  
pp. 156-164 ◽  
Author(s):  
Anatoly E. Martynyuk ◽  
Timothy E. Morey ◽  
Pekka M.J. Raatikainen ◽  
Christoph N. Seubert ◽  
Donn M. Dennis

Background Commonly used barbiturate anesthetics may significantly influence cardiac electrophysiologic characteristics. The authors evaluated thiopental (a thiobarbiturate) and methohexital (an oxybarbiturate), two compounds with similar physicochemical properties but different structures, to determine whether they have distinct effects on the major ionic currents that determine action potential duration (APD) in ventricular myocytes. Methods The effects of thiopental and methohexital (50 microM) on APD at 50% (APD50) and 90% (APD90) repolarization were studied in guinea pig and rabbit single ventricular myocytes using the patch-clamp technique in a whole-cell configuration. The ionic mechanisms underlying the APD changes were evaluated by measuring the anesthetics' effects on the L-type calcium inward current, the inward rectifier potassium current, and the delayed rectifier potassium current in guinea pig cells and on the transient outward potassium current in rabbit cells. Results Thiopental and methohexital caused opposite effects on APD. Whereas thiopental prolonged APD50 and APD90 in guinea pig and rabbit ventricular myocytes, methohexital shortened them. Thiopental markedly depressed both the inward and outward components of the inward rectifier potassium current, whereas methohexital caused minimal inhibition of the inward component and no change in the outward component. The delayed rectifier potassium current was inhibited by thiopental but significantly potentiated by methohexital. Neither thiopental nor methohexital significantly affected the transient outward potassium current or the L-type calcium inward current. Conclusions Despite their similar lipid solubilities, molecular weights, and pKa values, thiopental increased and methohexital decreased the APD in ventricular myocytes by predominantly inhibiting the inward rectifier potassium current and the delayed rectifier potassium current and by increasing the delayed rectifier potassium current, respectively. These characteristics suggest distinct structure-specific actions of barbiturates on the function of myocardial ionic channels.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Delin Wu ◽  
Linqing Jiang ◽  
Hongjin Wu ◽  
Shengqi Wang ◽  
Sidao Zheng ◽  
...  

Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood.Aim. The effects of GA on the delayed rectifier potassium current (IK), the rapidly activating (IKr) and slowly activating (IKs) components ofIK, and the HERG K+channel expressed in HEK-293 cells were investigated.Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to recordIK(IKr,IKs) and the HERG K+current.Results. GA (1, 5, and 10 μM) inhibitedIK(IKr,IKs) and the HERG K+current in a concentration-dependent manner.Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition ofIK(IKr,IKs) and HERG K+channel.


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