1.Regulation of Antiarrhythmic Drug Propafenone Effects on the C-type KV1.4 Potassium Channel by PHo and K+.
Zhiquan WANG ; Shimin WANG ; Jianjun LI ; Xuejun JIANG ; Neng WANG
Journal of Korean Medical Science 2009;24(1):84-91
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.
Animals
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Anti-Arrhythmia Agents/*pharmacology
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Hydrogen-Ion Concentration
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Inhibitory Concentration 50
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Kv1.4 Potassium Channel/*antagonists & inhibitors/metabolism
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Oocytes/drug effects/metabolism
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Patch-Clamp Techniques
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Potassium/*metabolism
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Potassium Channel Blockers/*pharmacology
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Propafenone/*pharmacology
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Xenopus laevis