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Crataegus extract blocks potassium currents in guinea pig ventricular cardiac myocytes
1Institut für Pharmakologie, Universität zu Köln, Germany. andreas.müller@uni-koeln.de
Insights
Crataegus extract prolongs cardiac action potential duration by blocking repolarizing potassium currents in ventricular myocytes. This mechanism, similar to antiarrhythmic drugs, may explain its therapeutic effects in heart failure.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Crataegus extract is clinically used for heart failure (NYHA II) in Germany.
- Its precise electrophysiological mechanisms remain largely unelucidated.
- Previous studies indicated effects on refractory period and action potential duration.
Purpose of the Study:
- To investigate the electrophysiological mechanism underlying the action potential duration increase caused by Crataegus extract.
- To determine the effects of Crataegus extract on specific ion currents in cardiac myocytes.
Main Methods:
- Utilized the patch-clamp technique on isolated guinea pig ventricular myocytes.
- Measured the impact of Crataegus extract on inward rectifier and delayed rectifier potassium currents.
- Assessed effects on the L-type calcium current to explore inotropic mechanisms.
Main Results:
- Crataegus extract demonstrated slight blockade of both delayed (25%) and inward rectifier (15%) potassium currents.
- This inhibition of repolarizing currents sufficiently explains the observed action potential duration prolongation.
- No significant influence of Crataegus extract on the L-type calcium current was detected.
Conclusions:
- Crataegus extract acts by blocking repolarizing potassium currents in ventricular myocytes.
- This action is comparable to Class III antiarrhythmic drugs, suggesting a basis for its antiarrhythmic properties.
- The positive inotropic effect is unlikely due to phosphodiesterase inhibition or beta-sympathomimetic activity.
Abstract:
Crataegus extract is used in cardiology for the treatment of mild to moderate heart failure (NYHA II) in Germany. However, little is known about the electrophysiological actions of Crataegus extract in the heart. Recently, it was shown that Crataegus extract prolongs the refractory period in isolated perfused hearts and increases action potential duration in guinea pig papillary muscle. It was the aim of this study to find out the mechanism of the increase in action potential duration caused by Crataegus extract. Using the patch-clamp technique, we measured the effects of Crataegus extract (10 mg/l; flavonoid content: 2.25%, total procyanidin content: 11.3 +/- 0.4%) on the inward rectifier and the delayed rectifier potassium current in isolated guinea pig ventricular myocytes. To get some insight into the mechanism underlying the positive inotropic effect of Crataegus extract, we also looked for effects on the L-type calcium current. Crataegus extract slightly blocked both the delayed and the inward rectifier potassium current. The inhibition amounted to 25% and about 15%, respectively. This amount of inhibition of these repolarising currents is sufficient to explain the prolongation of action potential duration caused by Crataegus extract. To our surprise we could not detect any influence of Crataegus extract on the L-type calcium current. In summary, our results show that Crataegus extract blocks repolarising potassium currents in ventricular myocytes. This effect is similar to the action of class III antiarrhythmic drugs and might be the basis of the antiarrhythmic effects described for Crataegus extract. Our measurements of the L-type calcium current indicate that Crataegus extract's positive inotropic effect is not caused by phosphodiesterase inhibition or a beta-sympathomimetic effect.