Effects of benzyltetrahydropalmatine on two components of the delayed rectifier K+ current in Guinea pig ventricular myocytes.
The effects of benzyltetrahydropalmatine (BTHP), a new class III antiarrhythmic agent, on the action potential in guinea pig papillary muscle and the rapidly activating component (I(Kr)) and the slowly activating component (I(Ks)) of the delayed rectifier potassium current (I(K)) in isolated guinea pig ventricular myocytes were investigated. The action potentials of papillary muscles were studied using a standard microelectrode technique, while the K(+) currents were recorded using the whole-cell patch clamp technique. The results showed that BTHP prolonged the action potential duration (APD) without altering other variables of the action potential in guinea pig papillary muscles. The 2 components of I(K) were blocked by BTHP (1 approximately 100 micromol x L(-1)) in time-, concentration-, voltage-, and specifically frequency-dependent fashion. The IC(50) value for blockade of I(Kr) was 13.5 micromol x L(-1), while the IC(50) value for blockade of I(Ks) was 9.3 micromol x L(-1). BTHP 30.0 micromol x L(-1) reduced I(Kr) and I(Kr,tail) by 31 +/- 4.3% and 36 +/- 4.7% (n = 6, p < 0.01) and decreased I(Ks) and I(Ks,tail) by 40 +/- 6.3% and 39 +/- 4.6% (n = 7, p < 0.01) respectively. BTHP accelerated their deactivation course by reducing the time constants of deactivation of I(Kr) and I(Ks). The activation kinetics of I(Kr) or I(Ks) were not affected by BTHP. It is concluded that BTHP prolonged the action potential duration with respect to its non-selective action on I(Kr) and I(Ks) in single guinea pig ventricular cell in a frequency-dependent fashion.
Li
Yang
Y
Department of Cardiology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China. liyang40@hotmail.com.
Fu
Li ying
Ly
Yao
Weixing
W
Xia
Guojin
G
Jiang
Mingxing
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010210:Papillary Muscles / Q000166:cytology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated
D000889:Anti-Arrhythmia Agents; D001600:Berberine Alkaloids; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C060778:benzyltetrahydropalmatine