Inhibitory effects of DDPH on two components of delayed rectifier potassium current in guinea pig ventricular cells.
OBJECTIVE
To study the effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxy-phenyl-ethylamino) propane hydro-chloride (DDPH) on the rapidly activating component (I(Kr)), and the slowly activating component (I(Ks)) of the delayed rectifier potassium current (I(K)) in guinea pig ventricular myocytes.


METHODS
Whole-cell patch clamp recording techniques.


RESULTS
DDPH (0.1-100 micromol/L) blocked the I(Kr) in a concentration-dependent manner. The IC50 (micromol/L) was 6.1 (95 % confidence limits: 2.8-13.5). IC50 (micromol/L) of DDPH blocking I(Ks) was 12.5 (95 % confidence limits: 4.8-32.2). DDPH (10 micromol/L) did not affect activation time constants and the voltage-dependent activation of both I(Kr) and I(Ks), the half-activation voltage (V1/2, mV) and slope factor (k, mV) were I(Kr): -23.5+/-2.4 and 8.1+/-2.2 [in presence of DDPH, P >0.05, compared with control, V1/2 (-21.7+/-0.8) and k (5.9+/-0.8)]; I(Ks): 27.1+/-0.7 and 16.6+/-0.8 [in presence of DDPH, P >0.05, compared with control, V1/2 (27.0+/-0.8) and k (14.9+/-0.9)]. DDPH slightly increased the deactivation time-constant of I(Kr) ( r) and I(Ks) ( s) at low concentration (<10 micromol/L). The inactivation of I(Kr) was significantly accelerated by DDPH.


CONCLUSIONS
DDPH inhibited both I(Kr) and I(Ks). The blockade was not due to its influence on activation, but the process of deactivation. The blocking of I(Kr) by DDPH was further associated with its acceleration the channel inactivation.
Zhong
Ning
N
Physiological Laboratory of Hypoxia, Shanghai Institute of Biological Sciences, Chinese Academy of Science, Shanghai 200031, China.
Fang
Qi-Zhi
QZ
Zhang
Yi
Y
Xia
Jing-Sheng
JS
Qian
Jia-Qing
JQ
Zhou
Zhao-Nian
ZN
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002469:Cell Separation; D051668:Delayed Rectifier Potassium Channels; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated
D000889:Anti-Arrhythmia Agents; D051668:Delayed Rectifier Potassium Channels; D010627:Phenethylamines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); C057485:1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane