Regulation of antiarrhythmic drug propafenone effects on the c-type Kv1.4 potassium channel by PHo and K+.
The effects of the antiarrhythmic drug propafenone at c-type kv1.4 channels in Xenopus laevis oocytes were studied with the two-electrode voltage-clamp technique. Defolliculated oocytes (stage V-VI) were injected with transcribed cRNAs of ferret Kv1.4 Delta N channels. During recording, oocytes were continuously perfused with control solution or propafenone. Propafenone decreased the currents during voltage steps. The block was voltage-, use-, and concentration- dependent manners. The block was increased with positive going potentials. The voltage dependence of block could be fitted with the sum of monoexponential and a linear function. Propafenone accelerated the inactivate of current during the voltage step. The concentration of half-maximal block (IC(50)) was 121 microM/L. With high, normal, and low extracellular potassium concentrations, the changes of IC(50) value had no significant statistical differences. The block of propafenone was PH- dependent in high-, normal- and low- extracellular potassium concentrations. Acidification of the extracellular solution to PH 6.0 increased the IC(50) values to 463 microM/L, alkalization to PH 8.0 reduced it to 58 microM/L. The results suggest that propafenone blocks the Kv1.4 Delta N channel in the open state and give some hints for an intracellular site of action.
Wang
Zhiquan
Z
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China. wangzhiquan1031@yahoo.com.cn
Wang
Shimin
S
Li
Jianjun
J
Jiang
Xuejun
X
Wang
Neng
N
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D051665:Kv1.4 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011405:Propafenone / Q000494:pharmacology*; D014982:Xenopus laevis
D000889:Anti-Arrhythmia Agents; D051665:Kv1.4 Potassium Channel; D026902:Potassium Channel Blockers; D011405:Propafenone; D011188:Potassium