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001-es BibID:	BIBFORM057405
Első szerző:	Váczi Krisztina (élettanász)
Cím:	9-Anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential / Krisztina Váczi, Bence Hegyi, Ferenc Ruzsnavszky, Kornél Kistamás, Balázs Horváth, Tamás Bányász, Péter P. Nánási, Norbert Szentandrássy, János Magyar
Dátum:	2015
ISSN:	0028-1298
Megjegyzések:	Understanding the role of ionic currents in shaping the cardiac action potential (AP) has great importance as channel malfunctions can lead to sudden cardiac death by inducing arrhythmias. Therefore, researchers frequently use inhibitors to selectively block a certain ion channel like 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC) for calcium-activated chloride current (ICl(Ca)). This study aims to explore which blocker is preferable to study ICl(Ca). Whole-cell voltage-clamp technique was used to record ICa,L, IKs, IKr and IK1, while action potentials were measured using sharp microelectrodes. DIDS- (0.2 mM) and 9-AC-sensitive (0.5 mM) currents were identical in voltage-clamp conditions, regardless of intracellular Ca(2+) buffering. DIDS-sensitive current amplitude was larger with the increase of stimulation rate and correlated well with the rate-induced increase of calcium transients. Both drugs increased action potential duration (APD) to the same extent, but the elevation of the plateau potential was more pronounced with 9-AC at fast stimulation rates. On the contrary, 9-AC did not influence either the AP amplitude or the maximal rate of depolarization (V max), but DIDS caused marked reduction of V max. Both inhibitors reduced the magnitude of phase-1, but, at slow stimulation rates, this effect of DIDS was larger. All of these actions on APs were reversible upon washout of the drugs. Increasing concentrations of 9-AC between 0.1 and 0.5 mM in a cumulative manner gradually reduced phase-1 and increased APD. 9-AC at 1 mM had no additional actions upon perfusion after 0.5 mM. The half-effective concentration of 9-AC was approximately 160 ?M with a Hill coefficient of 2. The amplitudes of ICa,L, IKs, IKr and IK1 were not changed by 0.5 mM 9-AC. These results suggest that DIDS is equally useful to study ICl(Ca) during voltage-clamp but 9-AC is superior in AP measurements for studying the physiological role of ICl(Ca) due to the lack of sodium channel inhibition. 9-AC has also no action on other ion currents (ICa,L, IKr, IKs, IK1); however, ICa,L tracings can be contaminated with ICl(Ca) when measured in voltage-clamp condition.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Calcium-activated chloride current Canine myocytes 9-Anthracene carboxylic acid DIDS Action potential Ion currents
Megjelenés:	Naunyn-Schmiedebergs Archives Of Pharmacology. - 388 : 1 (2015), p. 87-100. -
További szerzők:	Hegyi Bence (1987-) (élettanász) Ruzsnavszky Ferenc (1984-) (élettanász) Kistamás Kornél (1986-) (biológus) Horváth Balázs (1981-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Magyar János (1961-) (élettanász)
Pályázati támogatás:	PD101171 OTKA K100151 OTKA K101196 OTKA K109736 OTKA NK104331 OTKA TÁMOP-4.2.2.A-11/1/KONV-2012-0045 TÁMOP Élettan Kutatócsoport TÁMOP 4.2.4. A/2-11-1-2012-0001 TÁMOP
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