J Korean Med Sci.  2009 Feb;24(1):84-91. 10.3346/jkms.2009.24.1.84.

Regulation of Antiarrhythmic Drug Propafenone Effects on the C-type KV1.4 Potassium Channel by PHo and K+

• Wang Z
• Wang S
• Li J
• Jiang X
• Wang N

• KMID: 1794411
• DOI: http://doi.org/10.3346/jkms.2009.24.1.84

Abstract

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 techinique. 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 micrometer/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 IC50 values to 463 micrometer/L, alkalization to PH 8.0 reduced it to 58 micrometer/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.

Keyword

Potassium Channels; Anti-arrhythmic drug; Ion Channels, Voltage-Gated; Voltage Clamp; Membrane Currents

MeSH Terms

Animals
Anti-Arrhythmia Agents/*pharmacology
Hydrogen-Ion Concentration
Inhibitory Concentration 50
Kv1.4 Potassium Channel/*antagonists & inhibitors/metabolism
Oocytes/drug effects/metabolism
Patch-Clamp Techniques
Potassium/*metabolism
Potassium Channel Blockers/*pharmacology
Propafenone/*pharmacology
Xenopus laevis