Inhibitory effect of 1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenyl-ethylamino) propane hydrochloride on inward rectifier and delayed rectifier K+ currents in guinea pig ventricular myocytes.
OBJECTIVE
To study the effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenyl-ethylamino) propane hydrochloride (DDPH) on action potential (AP), inward rectifier K+ current (IK1), and delayed rectifier K+ current (IK) in isolated guinea pig ventricular myocytes.


METHODS
Whole cell patch-clamp recording techniques.


RESULTS
DDPH 0.1-100 mumol.L-1 decreased 50% duration of action potential (APD50) concentration-dependently. APD50 was shortened from (493 +/- 58) to (262 +/- 38) ms (n = 7 cells from 5 guinea pigs, P < 0.01) by DDPH 10 mumol.L-1. However, 90% duration of action potential (APD90) was increased by DDPH (> 1 mumol.L-1). At high concentration (> 10 mumol.L-1) DDPH decreased resting membrane potential (RP) and amplitude of action potential (APA). DDPH inhibited tail current of IK (IK.tail) concentration-dependently, 46% at 10 mumol.L-1 and 78% at 100 mumol.L-1. EC50 for DDPH inhibiting IK was 13.3 (11.6-16.7) mumol.L-1. DDPH also blocked IK1. DDPH at high concentration (> 10 mumol.L-1) shifted the reverse potential of IK1 positively. All the effects of DDPH were reversible after washout.


CONCLUSIONS
DDPH blocked both IK1 and IK current in guinea pig ventricular myocytes.
Zhong
N
N
Shanghai Institute of Physiology, Chinese Academy of Sciences, Shanghai 200031, China. nolannz@sunm.shcnc.ac.cn
Fang
Q Z
QZ
Zhang
Y
Y
Qian
J Q
JQ
Zhou
Z N
ZN
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002469:Cell Separation; D006168:Guinea Pigs; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D015221:Potassium Channels; C057485:1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane