Vernakalant activates human cardiac K2P17.1 background K+ channels.

Atrial fibrillation (AF) contributes significantly to cardiovascular morbidity and mortality. The growing epidemic is associated with cardiac repolarization abnormalities and requires the development of more effective antiarrhythmic strategies. Two-pore-domain K + channels stabilize the resting membrane potential and repolarize action potentials. Recently discovered K 2P 17.1 channels are expressed in human atrium and represent potential targets for AF therapy. However, cardiac electropharmacology of K 2P 17.1 channels remains to be investigated. This study was designed to elucidate human K 2P 17.1 regulation by antiarrhythmic drugs. Two-electrode voltage clamp and whole-cell patch clamp electrophysiology was used to record K 2P currents from Xenopus oocytes and Chinese hamster ovary (CHO) cells. The class III antiarrhythmic compound vernakalant activated K 2P 17.1 currents in oocytes an in mammalian cells (EC 50,CHO = 40 μM) in frequency-dependent manner. K 2P 17.1 channel activation by vernakalant was specific among K 2P channel family members. By contrast, vernakalant reduced K 2P 4.1 and K 2P 10.1 currents, in line with K 2P 2.1 blockade reported earlier. K 2P 17.1 open rectification characteristics and current–voltage relationships were not affected by vernakalant. The class I drug flecainide did not significantly modulate K 2P currents. In conclusion, vernakalant activates K 2P 17.1 background potassium channels. Pharmacologic K 2P channel activation by cardiovascular drugs has not been reported previously and may be employed for personalized rhythm control in patients with AF-associated reduction of K + channel function. [ABSTRACT FROM AUTHOR]