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1.

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
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2.

001-es BibID:BIBFORM030258
035-os BibID:WOS:000181565400020
Első szerző:Magyar János (élettanász)
Cím:Differential effects of fluoxetine enantiomers in mammalian neural and cardiac tissues / János Magyar, Zoltán Rusznák, Csaba Harasztosi, Ágnes Körtvély, Pál Pacher, Tamás Bányász, Csaba Pankucsi, László Kovács, Géza Szűcs, Péter P. Nánási, Valéria Kecskeméti
Dátum:2003
ISSN:1107-3756
Megjegyzések:Racemic fluoxetine is a widely used SSRI antidepressant compound having also anticonvulsant effect. In addition, it was shown that it blocked several types of voltage gated ion channels including neural and cardiac calcium channels. In the present study the effects of enantiomers of fluoxetine (R(-)-fluoxetine and S(+)-fluoxetine) were compared on neuronal and cardiac voltage-gated Ca2+ channels using the whole cell configuration of patch clamp techniques, and the anticonvulsant action of these enantiomers was also evaluated in a mouse epilepsy model. In isolated pyramidal neurons of the dorsal cochlear nucleus of the rat the effect of fluoxetine (S(+), R(-) and racemic) was studied on the Ca2+ channels by measuring peak Ba2+ current during ramp depolarizations. All forms of fluoxetine reduced the Ba2+ current of the pyramidal cells in a concentration-dependent manner, with a K, value of 22.3 +/- 3.6 muM for racemic fluoxetine. This value of K, was higher by one order of magnitude than found in cardiac myocytes with fluoxetine enantiomers (2.4 +/- 0.1 and 2.8 +/- 0.2 muM). Difference between the effects of the two enantiomers on neuronal Ba2+, current was observed only at 5 muM concentration: R(-)-fluoxetine inhibited 28 +/- 3% of the peak current, while S(+)-fluoxetine reduced the current by 18 +/- 2% (n=13, P<0.05). In voltage clamped canine ventricular cardiomyocytes both enantiomers of fluoxetine caused a reversible concentration-dependent block of the peak Ca2+ current measured at 0 mV. Significant differences between the two enantiomers in this blocking effect was observed at low concentrations only: S(+)-fluoxetine caused a higher degree of block than R(-)-fluoxetine (56.3 +/- 2.2% versus 49.1 +/- 2.2% and 95.5 +/- 0.9% versus 84.5 +/- 3.1% block with 3 and 10 &mu;M S(+) and R(-)-fluoxetine, respectively, P<0.05, n=5). Studied in current clamp mode, micromolar concentrations of fluoxetine shortened action potential duration of isolated ventricular cells, while higher concentrations also suppressed maximum velocity of depolarization and action potential amplitude. This shortening effect was significantly greater in the case of S(+) than R(-)-fluoxetine at 1 and 3 muM concentrations, whereas no differences in their effects on depolarization were observed. In pentylenetetrazole-induced mouse epilepsy model fluoxetine pretreatment significantly increased the 60 min survival rate, survival duration and seizure latency. These effects were more pronounced with the R(-) than the S(+) enantiomer. The results indicate that fluoxetine exerts much stronger suppressive effect on cardiac than neuronal calcium channels. At micromolar concentrations (between 1 and 10 muM) R(-)-fluoxetine is more effective than the S(+) enantiomer on neuronal, while less effective on cardiac calcium channels. The stronger anticonvulsant effect of the R(-) enantiomer may, at least partially, be explained by these differences. Used as an antidepressant or anticonvulsant drug, less severe cardiac side-effects are anticipated with the R(-) enantiomer.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:International Journal of Molecular Medicine. - 11 : 4 (2003), p. 535-542. -
További szerzők:Rusznák Zoltán (1965-) (élettanász) Harasztosi Csaba Körtvély Ágnes Pacher Pál Bányász Tamás (1960-) (élettanász) Pankucsi Csaba (farmakológus) Kovács László (1939-) (élettanász) Szűcs Géza (1948-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Kecskeméti Valéria
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3.

001-es BibID:BIBFORM030256
035-os BibID:WOS:000178499200009
Első szerző:Magyar János (élettanász)
Cím:Electrophysiological effects of risperidone in mammalian cardiac cells / János Magyar, Tamás Bányász, Zsolt Bagi, Pál Pacher, Norbert Szentandrássy, László Fülöp, Valéria Kecskeméti, Péter P. Nánási
Dátum:2002
ISSN:0028-1298
Megjegyzések:In this study, the effects of risperidone, the widely used antipsychotic drug, on isolated canine ventricular myocytes and guinea-pig papillary muscles were analyzed using conventional microelectrode and whole cell voltage-clamp techniques. Risperidone concentration-dependently lengthened action potential duration in guinea-pig papillary muscles (EC50=0.29 +/- 0.02 muM) and single canine ventricular myocytes (EC50=0.48 +/- 0.14 muM). This effect was reversible, showed reverse rate dependence, and it was most prominent on the terminal portion of repolarization. No significant effect of risperidone on the resting membrane potential, action potential amplitude or maximum rate of depolarization was observed. In voltage-clamped canine ventricular myocytes risperidone caused concentration-dependent block of the rapid component of the delayed rectifier K+ current (1(Kr)), measured as outward current tails at -40 mV with an IC50 of 0.92 +/- 0.26 muM. Suppression of I-Kr was not associated with changes in activation or deactivation kinetics. High concentration of risperidone (10 muM) suppressed also the slow component of the delayed rectifier K+ current (I-Ks) by 9.6 +/- 1.5% at +50 mV. These effects of risperidone developed rapidly and were readily reversible. Risperidone had no significant effect on the amplitude of other K+ currents (I-K1 and I-to). The inhibition of cardiac I-Kr current by risperidone may explain the cardiac side-effects observed occasionally with the drug. Our results suggest that risperidone displays class III antiarrhythmic properties, and as such, may produce QTc prolongation, especially in patients with long QT syndrome. Therefore, in psychotic patients having also cardiac disorders, ECG control may be suggested during risperidone therapy.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 366 : 4 (2002), p. 350-356. -
További szerzők:Bányász Tamás (1960-) (élettanász) Bagi Zsolt (1974-) (orvos) Pacher Pál Szentandrássy Norbert (1976-) (élettanász) Fülöp László (1976-) (kardiológus) Kecskeméti Valéria Nánási Péter Pál (1956-) (élettanász)
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4.

001-es BibID:BIBFORM030244
035-os BibID:WOS:000224528800006
Első szerző:Magyar János (élettanász)
Cím:Effects of norfluoxetine on the action potential and transmembrane ion currents in canine ventricular cardiomyocytes / János Magyar, Norbert Szentandrassy, Tamás Banyasz, Valéria Kecskemeti, Péter P. Nanasi
Dátum:2004
ISSN:0028-1298
Megjegyzések:Norfluoxetine is the most important active metabolite of the widely used antidepressant compound fluoxetine. Although the cellular electrophysiological actions of fluoxetine are well characterized in cardiac cells, little is known about the effects of its metabolite. In this study, therefore, the effects of norfluoxetine on action potential (AP) configuration and transmembrane ion currents were studied in isolated canine cardiomyocytes using the whole cell configuration of patch clamp techniques. Micromolar concentrations of norfluoxetine (1-10 muM) modified AP configuration: amplitude and duration of the AP and maximum velocity of depolarization were decreased in addition to depression of the plateau and elimination of the incisura of AP. Voltage clamp experiments revealed a concentration-dependent suppression of both L-type Ca2+ current, I-Ca (EC50=1.13 +/-10.08 muM) and transient outward K+ current, I-to (EC50=1.19+/-0.17 muM) having Hill coefficients close to unity. The midpoint potential of the steady-state inactivation of I-Ca was shifted from -20.9+/-0.75 mV to -27.7 +/-1.35 mV by 3 muM norfluoxetine (P<0.05, n=7). No such shift in the steady-state inactivation curve was observed in the case of I-to. Similarly, norfluoxetine caused no change in the steady-state current-voltage relationship of the membrane or in the density of the inward rectifier K+ current, I-Kl. All these effects of norfluoxetine developed rapidly and were fully reversible. Comparing present results with those obtained previously with fluoxetine, it can be concluded that norfluoxetine displays stronger suppression of cardiac ion channels than fluoxetine. Consequently, the majority of the cardiac side effects observed during fluoxetine treatment are likely to be attributed to its metabolite norfluoxetine.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 370 : 3 (2004), p. 203-210. -
További szerzők:Szentandrássy Norbert (1976-) (élettanász) Bányász Tamás (1960-) (élettanász) Kecskeméti Valéria Nánási Péter Pál (1956-) (élettanász)
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5.

001-es BibID:BIBFORM030266
035-os BibID:WOS:000084701100010
Első szerző:Pacher Pál
Cím:Electrophysiological effects of fluoxetine in mammalian cardiac tissues / Pál Pacher, János Magyar, Péter Szigligeti, Tamás Bányász, Csaba Pankucsi, Zsuzsanna Korom, Zoltán Ungvári, Valéria Kecskeméti, Péter P. Nánási
Dátum:2000
ISSN:0028-1298
Megjegyzések:Fluoxetine is a widely used antidepressant compound having selective serotonin reuptake inhibitor properties. In this study, the actions of fluoxetine were analyzed in guinea pig, rat, rabbit and canine ventricular myocardiac preparations using conventional microelectrode and whole cell voltage clamp techniques. Low concentrations of fluoxetine (1-10 mu mol/l) caused significant shortening of action potential duration (APD) and depression of the plateau potential in guinea pig and rabbit papillary muscles and single canine ventricular myocytes. In rat papillary muscle, APD was not affected by fluoxetine (up to 100 mu mol/l), however, the drug decreased the force of contraction with EC50 of 10 mu mol/l. Fluoxetine (10 mu mol/l) also decreased the maximum velocity of depolarization and action potential overshoot in each species studied. At this concentration no effect was observed on the resting membrane potential; high concentration (100 mu mol/l), however, caused depolarization. In voltage clamped canine ventricular myocytes, fluoxetine caused concentration-dependent block of the peak Ca2+ current at 0 mV with EC50 Of 5.4+/-0.94 mu mol/l and Hill coefficient of 1.1+/-0.14 (n=6). In addition, 10 mu mol/l fluoxetine shifted the midpoint of the steady-state inactivation curve of the Ca2+ current from -20.7+/-0.65 to -26.7+/-1 mV (P<0.001, n=8) without changing its slope factor. These effects of fluoxetine developed rapidly and were fully reversible. Fluoxetine did not alter voltage-dependence of activation or time constant for inactivation of I-Ca. Fluoxetine had no effect on the amplitude of K+ currents (I-K1 and I-to). The inhibition of cardiac Ca2+ and Na+ channels by fluoxetine may explain most cardiac side effects observed occasionally with the drug. Our results suggest that fluoxetine may have antiarrhythmic (class I + IV type), as well as proarrhythmic properties (due to impairment of atrioventricular or intraventricular conduction and shortening of repolarization). Therefore, in depressed patients with cardiac disorders, ECG control may be suggested during fluoxetine therapy.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 361 : 1 (2000), p. 67-73. -
További szerzők:Magyar János (1961-) (élettanász) Szigligeti Péter Bányász Tamás (1960-) (élettanász) Pankucsi Csaba (farmakológus) Korom Zsuzsanna Ungvári Zoltán Kecskeméti Valéria Nánási Péter Pál (1956-) (élettanász)
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6.

001-es BibID:BIBFORM037321
Első szerző:Szentandrássy Norbert (élettanász)
Cím:Effects of rosiglitazone on the configuration of action potentials and ion currents in canine ventricular cells / Szentandrássy N., Harmati G., Bárándi L., Simkó J., Horváth B., Magyar J., Bányász T., Lőrincz I., Szebeni A., Kecskeméti V., Nánási P.P.
Dátum:2011
ISSN:0007-1188
Megjegyzések:BACKGROUND AND PURPOSEIn spite of its widespread clinical application, there is little information on the cellular cardiac effects of the antidiabetic drug rosiglitazone in larger experimental animals. In the present study therefore concentration-dependent effects of rosiglitazone on action potential morphology and the underlying ion currents were studied in dog hearts.EXPERIMENTAL APPROACHStandard microelectrode techniques, conventional whole cell patch clamp and action potential voltage clamp techniques were applied in enzymatically dispersed ventricular cells from dog hearts.KEY RESULTSAt concentrations ?10 mM rosiglitazone decreased the amplitude of phase-1 repolarization, reduced the maximum velocity of depolarization and caused depression of the plateau potential. These effects developed rapidly and were readily reversible upon washout. Rosiglitazone suppressed several transmembrane ion currents, oncentration-dependently, under conventional voltageclamp conditions and altered their kinetic properties. The EC50 value for this inhibition was 25.2 ? 2.7 mM for the transient outward K+ current (Ito), 72.3 ? 9.3 mM for the rapid delayed rectifier K+ current (IKr) and 82.5 ? 9.4 mM for the L-type Ca2+ current (ICa) with Hill coefficients close to unity. The inward rectifier K+ current (IK1) was not affected by rosiglitazone up to concentrations of 100 mM. Suppression of Ito, IKr, and ICa was confirmed also under action potential voltage clamp conditions.CONCLUSIONS AND IMPLICATIONSAlterations in the densities and kinetic properties of ion currents may carry serious pro-arrhythmic risk in case of overdose with rosiglitazone, especially in patients having multiple cardiovascular risk factors, like elderly diabetic patients.
Tárgyszavak:Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban
antidiabetic agents
rosiglitazone
dog cardiomyocytes
action potential
ion currents
Megjelenés:British Journal Of Pharmacology 163 : 3 (2011), p. 499-509. -
További szerzők:Harmati Gábor (1983-) (élettanász) Bárándi László (1984-) (élettanász) Simkó József (1974-) (belgyógyász, kardiológus) Horváth Balázs (1981-) (élettanász) Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Lőrincz István (1950-) (belgyógyász, kardiológus) Szebeni Andrea Kecskeméti Valéria Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
A feszültségfüggő K-csatornák szerepe excitábilis sejtekben
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