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001-es BibID:BIBFORM049179
035-os BibID:PMID:23588116 WOS:000319508800002
Első szerző:Kistamás Kornél (biológus)
Cím:Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes / Kornél Kistamás, Norbert Szentandrássy, Bence Hegyi, Ferenc Ruzsnavszky, Krisztina Váczi, László Bárándi, Balázs Horváth, Andrea Szebeni, János Magyar, Tamás Bányász, Valéria Kecskeméti, Péter P. Nánási
Dátum:2013
ISSN:0014-2999
Megjegyzések:Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ?3 ?M. Action potentials were shortened by pioglitazone at concentrations ?10 ?M, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K+ current (Ito), the L-type Ca2+ current (ICa), the rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), and the inward rectifier K+ current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ?3 ?M, ICa, IKr, IKs at concentrations ?10 ?M, while IK1 at concentrations ?30 ?M. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K+ current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 ?M pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Antidiabetic agents
Pioglitazone
Dog cardiomyocytes
Action potentials
Ion currents
Megjelenés:European Journal of Pharmacology. - 710 : 1-3 (2013), p. 10-19. -
További szerzők:Szentandrássy Norbert (1976-) (élettanász) Hegyi Bence (1987-) (élettanász) Ruzsnavszky Ferenc (1984-) (élettanász) Váczi Krisztina (1987-) (élettanász) Bárándi László (1984-) (élettanász) Horváth Balázs (1981-) (élettanász) Szebeni Andrea Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Kecskeméti Valéria Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:K100151
OTKA
NK104331
OTKA
K101196
OTKA
PD101171
OTKA
TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
Élettan Kutatócsoport
Internet cím:Szerző által megadott URL
DOI
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2.

001-es BibID:BIBFORM030245
035-os BibID:WOS:000220687400004
Első szerző:Magyar János (élettanász)
Cím:Effects of terpenoid phenol derivatives on calcium current in canine and human ventricular cardiomyocytes / János Magyar, Norbert Szentandrassy, Tamás Banyasz, László Fülöp, András Varro, Péter P. Nanasi
Dátum:2004
ISSN:0014-2999
Megjegyzések:Concentration-dependent (10-1000 muM) effects of terpenoid phenol derivatives were studied on L-type Ca2+ current in isolated canine and human ventricular cardiomyocytes using the whole-cell configuration of patch clamp technique. Carvacrol, thymol and eugenol suppressed peak Ca2+ current at +5 mV, having EC50 values and Hill coefficients of 98 +/- 11, 158 +/- 7 and 187 +/- 15 muM and 1.42 +/- 0.05, 2.96 +/- 0.43 and 1.6 +/- 0.1, respectively, in canine myocytes. Zingerone displayed a weak effect (estimated EC50: 2 +/- 0.37 mM, Hill coefficient: 0.73 +/- 0.07), while vanillin and guaiacol failed to substantially modify Ca2+ current up to the concentration of I mM. In addition to tonic block, thymol and carvacrol, but not eugenol, evoked marked rate-dependent block at 2 Hz. Carvacrol and eugenol accelerated inactivation of Ca2+ current and caused leftward shift in the voltage dependence of steady-state inactivation without altering activation kinetics. Carvacrol, but not eugenol, increased the time constant of recovery from inactivation. These effects of carvacrol and eugenol developed rapidly and were largely reversible. In myocytes isolated from undiseased human hearts, the effect of carvacrol was similar to that observed in canine cells. It is concluded that suppression of cardiac Ca2+ currents by phenol derivatives is influenced by the substituent in the benzene ring, and the blocking effect of these drugs may involve interactions with the inactivation machinery of the channel. (C) 2004 Elsevier B.V. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:European Journal of Pharmacology. - 487 : 1-3 (2004), p. 29-36. -
További szerzők:Szentandrássy Norbert (1976-) (élettanász) Bányász Tamás (1960-) (élettanász) Fülöp László (1976-) (kardiológus) Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
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