[Inhibition of transmembrane  K(+) currents in mammalian ventricular myocytes by antiarrhythmic agent RP62719].
The effect of RP62719 on the inward rectifier K(+) current (I(K1)),transient outward K(+) current (I(to)) and delayed outward K(+) current (I(K)) in isolated cardiac myocytes was determined using the whole cell patch clamp technique in guinea pig and dog. RP62719 decreased I(K1) with an inhibitory concentration 50 (IC(50) ) of 5.0+/-1.0 micromol/L at -100 mV in guinea pig ventricular cells. In dog ventricular myocytes, RP62719 inhibited Ito by 84+/-4.4% with an IC(50) of 1.2+/-0.51 micromol/L at +40 mV. In guinea pig ventricular cells, RP62719 decreased I(K): I(Kstep) by 50.0+/-8.3%%and I(Ktail) by 56.0+/-4.9% at +40 mV, respectively. RP62719 inhibited I(Kstep) with an IC(50) of 4.2+/-0.8 micromol/L and I(Ktail) with an IC(50) of 3.3+/-0.75 micromol/L. Thus it is suggested that the ionic mechanism of antiarrhymic effect by RP62719 may be due to its inhibition of I(K1),I(to) and I(K).
Li
Y R
YR
Department of Physiology, Harbin Medical University, Harbin 150086, China.
Yang
B F
BF
Xu
C Q
CQ
Zhou
J
J
Yang
Y B
YB
Zhang
J Y
JY
Sun
M Z
MZ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002469:Cell Separation; D002839:Chromans / Q000494:pharmacology*; D004285:Dogs; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D020128:Inhibitory Concentration 50; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D002839:Chromans; D010880:Piperidines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C063899:terikalant