title: Inhibitory effects of DDPH on two components of delayed rectifier potassium current in guinea pig ventricular cells.
abstract: 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.
authors.affiliation: Physiological Laboratory of Hypoxia, Shanghai Institute of Biological Sciences, Chinese Academy of Science, Shanghai 200031, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhong
authors.forename: Qi-Zhi
authors.initials: QZ
authors.lastname: Fang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing-Sheng
authors.initials: JS
authors.lastname: Xia
authors.forename: Jia-Qing
authors.initials: JQ
authors.lastname: Qian
authors.forename: Zhao-Nian
authors.initials: ZN
authors.lastname: Zhou
mesh_terms: 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
chemical_list: 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