Properties of several repolarizing potassium currents in atrial cadiomyocytes isolated from dogs in sinus rhythm and atrial fibrillation
█ Original article
Kohajda Zsófia1, Kristóf Attila1, Horváth András2, Juhász Viktor2, Sághy László3, Virág László2, Baczkó István2, Fazekas Tamás4, Varró András1,2, Jost Norbert1,2
1MTA-SZTE, Keringésfarmakológiai Kutatócsoport, Szeged
2SZTE, Általános Orvostudományi Kar, Farmakológiai és Farmakoterápiai Intézet, Szeged
3SZTE, Általános Orvostudományi Kar, II. sz. Belgyógyászati Klinika és Kardiológiai Központ, Szeged
4SZTE, Általános Orvostudományi Kar, I.sz. Belgyógyászati Klinika, Szeged
Aims: The aim of the present study was to investigate the properties of three repolarizing potassium currents which contribute to atrial fibrillation (AF) – induced electrical remodelling, i.e. the transient outward (Ito), inward rectifier (IK1) and acetylcholine-sensitive (IK,ACh) potassium currents in isolated atrial myocytes obtained from dogs either with sinus rhythm (SR) or following chronic atrial tachypacing (400/min) AF-dogs.
Methods: Atrial remodelling and AF were induced by chronic (4-6 weeks of) right atrial tachypacing (400/min) in dogs. Transmembrane ionic currents were measured by applying the whole-cell patch clamp technique at 37°C.
Results: The Ito current was slightly downregulated in AF cells when compared with that recorded in SR cells. IK1 current was not statistically significant different in AF and SR cells. IK,ACh was activated by carbachol (CCh; 2 µM). In SR, CCh activated a large current either in inward or outward directions. The selective IK,ACh inhibitor tertiapin (10 nM) blocked the outward CCh-induced current by 61%. In atrial myocytes isolated from dogs with AF, the presence of a constitutively active IK,ACh was observed, blocked by 59% with 10 nM tertiapin. However, in ’AF atrial myocytes’, CCh activated an additional, significant ligand-dependent and tertiapin-sensitive IK,ACh current.
Conclusions: The presence of the constitutively active IK,ACh in atrial myocytes from AF dogs shows that electrical remodeling truly developed in this model. The IK,ACh current (both ligand-dependent and constitutively active) seems to play a significant role in canine atrial electrical remodeling, and may be a promising atrial selective drug target for suppressing AF.