Ionic mechanisms responsible for the antiarrhythmic action of dehydroevodiamine in guinea-pig isolated cardiomyocytes.
1. Dehydroevodiamine alkaloid (DeHE), an active ingredient of a Chinese herbal medicine Wu-Chu-Yu (Evodiae frutus), has been shown to decrease aterial blood pressure in experimental animals and prolong action potential duration in cardiac cells. The aim of the present study was to explore the ionic basis of its possible antiarrhythmic effects. 2. Guinea-pig atrial and ventricular myocytes were isolated enzymatically and the ionic currents were recorded under whole-cell patch-clamp with single suction pipettes. 3. DeHE at a concentration of 0.1 microM inhibited reversibly the time-dependent outward K current (delayed rectifier, Ik) and the Na-dependent inward current (INa). 4. In low-K (1 mM) and high-Ca (9 mM) solution, DeHE also depressed the delayed afterdepolarizations (DAD) and the transient inward current (Iti) induced by 2 microM strophanthidin. On the other hand, DeHE occasionally induced early afterdepolarizations and slow response action potentials at a depolarized level. 5. At higher concentrations (1 microM and above), the L-type Ca current (ICa,L) was moderately inhibited. 6. The present findings indicate that DeHE may depress triggered arrhythmias in Ca-overloaded guinea-pig cardiac myocytes through its inhibitory actions on INa, Iti and, to a smaller extent, ICa. DeHE may also exert class III antiarrhythmic effect through a reduction of outward K currents (Ik) across the sarcolemma.
Loh
S H
SH
Institute of Pharmacology, National Defence Medical Centre, Taipei, Taiwan.
Lee
A R
AR
Huang
W H
WH
Lin
C I
CI
D000200:Action Potentials / Q000187:drug effects*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D011188:Potassium / Q000502:physiology; D012964:Sodium / Q000502:physiology
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; C028633:dehydroevodiamine; D012964:Sodium; D011188:Potassium; D002118:Calcium