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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2010; 56(1): 41-53


Atp-dependent potassium channelopener flocalin regulates cardiacexcitability

O.I. Voitychuk, О.О. Moibenko, Y.M. Shuba.

    International Center of Molecular Physiology;O.O.Bogomoletz Institute of Physiology, National Academyof Sciences of Ukraine, Kyiv


Abstract

ATP-sensitive potassium (K) channels activated by decrease in ATP/ADP ratio link cellular membrane potential with excit­ability, energy balance and metabolism. Under pathologic conditions of hypoxia and ischemia activation of plasma membrane KAT P channels reduces cell excitability and decreases carcium entry producing cytoprotective effect. In the current work we studied effects of a new fluorine containing pinacidil analogue flocalin on excitability of native cultured cardiomyo-cytes of neonatal rats and on activity of recombinant car-diospecific KATP channel in HEK-293 cells with stable heter­ologous expression of forming subunits Kir6.2 and SUR2A (HEK-293 6.2/2A). It was found that 5 uM flocalin induces reversible hyperpolarization and significant shortening of ac­tion potential (AP) in atrial, ventricular and spontaneously contracting neonatal cardiomyocytes. Atrial and ventricular epicardial cells showed decrease in amplitude and AP upstroke velocity. Flocalin significantly reduced contraction frequency and reversibly decreased resting diastolic potential of sponta­neously contracting cardiomyocytes. In HEK-293 6.2/2 cells flocalin dose-dependently activated time-independent K+ current with weak inward rectification through heterogously expressed KATP channels. Half-maximal flocalin concentration of current activation equals 8.8 uM and curve slope factor suggests positive cooperativity of flocalin binding to KATP channels. Our data show that flocalin is indeed an effective inhibitor of electrical and contractile activity of cardiomyo-cytes due to opening of cardiospecific KAT P channels and this property substantially mediates cardioprotection.

Keywords: neonatal cardiomyocytes, HEK-293 cells, ATP-sensitive potassium channels, resting potential, action poten-tial, flocalin

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