Electrophysiological effects of changrolin, an anti-arrhythmic agent derived from Dichroa febrifuga, on guinea-pig and rabbit heart cells.
1. The electrophysiological effects of changrolin (CRL), a Chinese anti-arrhythmic drug derived from a traditional antimalarial plant, were examined using the whole-cell patch-clamp method on single cells isolated from guinea-pig and rabbit hearts. 2. At a clinically relevant concentration of 50 mumol/L changrolin inhibited ICa by 19.3 +/- 6.0% and 17.3 +/- 2.6% in guinea-pig and rabbit ventricular cells, respectively. The voltage-dependent channel availability curve was not affected. The CRL effect was enhanced to a small extent during a repetitive stimulation at 2 Hz. 3. INa was resistant to CRL and the channel availability curve was also unaffected. A small use-dependent inhibition was observed only when the INa was elicited at 5 Hz in the presence of 300 mumol/L CRL. 4. At 50 mumol/L, CRL did not affect the time-independent inward rectifier and the delayed rectifier K+ currents (IK1 and IK, respectively), but inhibited the transient outward current (ITO) by 17.7 +/- 2.4%. Changrolin significantly shortened the action potential duration in both guinea-pig and rabbit ventricular cells. 5. In conclusion, CRL inhibits ICa and ITO but has little effect on INa.
Lu
L L
LL
Department of Physiology, Kyoto Prefectural University of Medicine, Japan.
Habuchi
Y
Y
Tanaka
H
H
Morikawa
J
J
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016275:Atrial Function; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D011817:Rabbits; D013045:Species Specificity; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D004365:Drugs, Chinese Herbal; D011799:Quinazolines; D011188:Potassium; C022128:changrolin