The effects of paeonol on the electrophysiological properties of cardiac ventricular myocytes.
Previous studies have shown that "Mudanpi", a Chinese herbal medicine, has a significant cardioprotective effect against myocardial ischaemia. Based on these findings we hypothesised that paeonol, the main component of Mudanpi, might have an effect on the cellular electrophysiology of cardiac ventricular myocytes. The effects of paeonol on the action potential and ion channels of cardiac ventricular myocytes were studied using the standard whole-cell configuration of the patch-clamp technique. Ventricular myocytes were isolated from the hearts of adult guinea-pig by enzymic dispersion. The myocytes were continuously perfused with various experimental solutions at room temperature and paeonol applied in the perfusate. Action potentials and membrane currents were recorded using both current and voltage clamp modes of the patch-clamp technique. Paeonol, at concentrations 160 microM and 640 microM, decreased the action potential upstroke phase, an action associated with the blockade of the voltage-gated, fast sodium channel. The effects of paeonol on both action potential and Na(+) current were concentration dependent. Paeonol had a high affinity for inactivated sodium channels. Paeonol also shortened the action potential duration, in a manner not associated with the blockade of the calcium current, or the enhancement of potassium currents. These findings suggest that paeonol, and therefore Mudanpi, may possess antiarrhythmic activity, which may confer its cardioprotective effects.
Ma
Yu-ling
YL
Department of Pharmacology, United Medical and Dental Schools, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. y.ma@reading.ac.uk
Bates
Susan
S
Gurney
Alison M
AM
D000098:Acetophenones / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006168:Guinea Pigs; D006352:Heart Ventricles; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects
D000098:Acetophenones; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C013638:paeonol