Cardiovascular pharmacology of K2P 17.1 (TASK-4, TALK-2) two-pore-domain K+ channels

Naunyn-Schmiedeberg's Archives of Pharmacology
Ingo StaudacherDierk Thomas

Abstract

K2P17.1 (TASK-4, TALK-2) potassium channels are expressed in the heart and represent potential targets for pharmacological management of atrial and ventricular arrhythmias. Reduced K2P17.1 expression was found in atria and ventricles of heart failure (HF) patients. Modulation of K2P17.1 currents by antiarrhythmic compounds has not been comprehensively studied to date. The objective of this study was to investigate acute effects of clinically relevant antiarrhythmic drugs on human K2P17.1 channels to provide a more complete picture of K2P17.1 electropharmacology. Whole-cell patch clamp and two-electrode voltage clamp electrophysiology was employed to study human K2P17.1 channel pharmacology. K2P17.1 channels expressed in Xenopus laevis oocytes were screened for sensitivity to antiarrhythmic drugs, revealing significant activation by propafenone (+ 296%; 100 μM), quinidine (+ 58%; 100 μM), mexiletine (+ 21%; 100 μM), propranolol (+ 139%; 100 μM), and metoprolol (+ 17%; 100 μM) within 60 min. In addition, the currents were inhibited by amiodarone (- 13%; 100 μM), sotalol (- 10%; 100 μM), verapamil (- 21%; 100 μM), and ranolazine (- 8%; 100 μM). K2P17.1 channels were not significantly affected by ajmaline and carvedilol. Concentrat...Continue Reading

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Citations

Aug 30, 2021·European Journal of Pharmacology·Michiko Nakamura, Il-Sung Jang

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Methods Mentioned

BETA
coronary artery bypass
electrophoresis
protein assay
transfections

Software Mentioned

Prism
Origin
GraphPad
PCLAMP
ImageJ
Excel

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