Search

Your search keyword '"Harmati, G"' showing total 5 results
Start Over Author "Harmati, G" Topic heart ventricles
5 results on '"Harmati, G"'

1. Effects of β-adrenoceptor stimulation on delayed rectifier K(+) currents in canine ventricular cardiomyocytes.

Author

Harmati G, Bányász T, Bárándi L, Szentandrássy N, Horváth B, Szabó G, Szentmiklósi JA, Szénási G, Nánási PP, and Magyar J

Subjects
Adrenergic beta-1 Receptor Antagonists pharmacology, Animals, Cells, Cultured, Cyclic AMP analogs & derivatives, Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors, Cyclic AMP-Dependent Protein Kinases metabolism, Dogs, Heart Ventricles cytology, Heart Ventricles metabolism, Imidazoles pharmacology, Isoproterenol pharmacology, Kinetics, Metoprolol pharmacology, Myocytes, Cardiac metabolism, Patch-Clamp Techniques, Protein Kinase Inhibitors pharmacology, Signal Transduction drug effects, Single-Cell Analysis, Action Potentials drug effects, Adrenergic beta-Agonists pharmacology, Delayed Rectifier Potassium Channels metabolism, Heart Ventricles drug effects, Myocytes, Cardiac drug effects, Receptors, Adrenergic, beta-1 metabolism
Abstract

Background and Purpose: While the slow delayed rectifier K(+) current (I(Ks)) is known to be enhanced by the stimulation of β-adrenoceptors in several mammalian species, phosphorylation-dependent regulation of the rapid delayed rectifier K(+) current (I(Kr)) is controversial., Experimental Approach: In the present study, therefore, the effect of isoprenaline (ISO), activators and inhibitors of the protein kinase A (PKA) pathway on I(Kr) and I(Ks) was studied in canine ventricular myocytes using the whole cell patch clamp technique., Key Results: I (Kr) was significantly increased (by 30-50%) following superfusion with ISO, forskolin or intracellular application of PKA activator cAMP analogues (cAMP, 8-Br-cAMP, 6-Bnz-cAMP). Inhibition of PKA by Rp-8-Br-cAMP had no effect on baseline I(Kr). The stimulating effect of ISO on I(Kr) was completely inhibited by selective β₁-adrenoceptor antagonists (metoprolol and CGP-20712A), by the PKA inhibitor Rp-8-Br-cAMP and by the PKA activator cAMP analogues, but not by the EPAC activator 8-pCPT-2'-O-Me-cAMP. In comparison, I(Ks) was increased threefold by the activation of PKA (by ISO or 8-Br-cAMP), and strongly reduced by the PKA inhibitor Rp-8-Br-cAMP. The ISO-induced enhancement of I(Ks) was decreased by Rp-8-Br-cAMP and completely inhibited by 8-Br-cAMP., Conclusions and Implications: The results indicate that the stimulation of β₁-adrenoceptors increases I(Kr), similar to I(Ks), via the activation of PKA in canine ventricular cells., (© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.)

Published
2011
Full Text
View/download PDF

2. Analysis of the contribution of I(to) to repolarization in canine ventricular myocardium.

Author

Virág, L, Jost, N, Papp, R, Koncz, I, Kristóf, A, Kohajda, Z, Harmati, G, Carbonell-Pascual, B, Ferrero Jr, JM, Papp, JG, Nánási, PP, Varró, A, Virág, L, Kristóf, A, Ferrero, J M Jr, Papp, J G, Nánási, P P, and Varró, A

Subjects
CARDIOMYOPATHIES, POTASSIUM, DOFETILIDE, ACTION potentials, VOLTAGE-clamp techniques (Electrophysiology), MICROELECTRODES, COMPUTER simulation, CELL metabolism, HEART metabolism, POTASSIUM metabolism, ANIMAL experimentation, BENZOPYRANS, CELLS, COMPARATIVE studies, CYTOLOGICAL techniques, DOGS, HEART ventricles, HEART conduction system, RESEARCH methodology, MEDICAL cooperation, MYOCARDIUM, PHENETHYLAMINES, RESEARCH, SULFONAMIDES, EVALUATION research, POTASSIUM antagonists, PHARMACODYNAMICS, PHYSIOLOGY
Abstract

Background and Purpose: The contribution of the transient outward potassium current (I(to)) to ventricular repolarization is controversial as it depends on the experimental conditions, the region of myocardium and the species studied. The aim of the present study was therefore to characterize I(to) and estimate its contribution to repolarization reserve in canine ventricular myocardium.Experimental Approach: Ion currents were recorded using conventional whole-cell voltage clamp and action potential voltage clamp techniques in canine isolated ventricular cells. Action potentials were recorded from canine ventricular preparations using microelectrodes. The contribution of I(to) to repolarization was studied using 100 µM chromanol 293B in the presence of 0.5 µM HMR 1556, which fully blocks I(Ks).Key Results: The high concentration of chromanol 293B used effectively suppressed I(to) without affecting other repolarizing K(+) currents (I(K1), I(Kr), I(p)). Action potential clamp experiments revealed a slowly inactivating and a 'late' chromanol-sensitive current component occurring during the action potential plateau. Action potentials were significantly lengthened by chromanol 293B in the presence of HMR 1556. This lengthening effect induced by I(to) inhibition was found to be reverse rate-dependent. It was significantly augmented after additional attenuation of repolarization reserve by 0.1 µM dofetilide and this caused the occurrence of early afterdepolarizations. The results were confirmed by computer simulation.Conclusions and Implications: The results indicate that I(to) is involved in regulating repolarization in canine ventricular myocardium and that it contributes significantly to the repolarization reserve. Therefore, blockade of I(to) may enhance pro-arrhythmic risk. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

3. Effects of rosiglitazone on the configuration of action potentials and ion currents in canine ventricular cells.

Author

Szentandrássy, N, Harmati, G, Bárándi, L, Simkó, J, Horváth, B, Magyar, J, Bányász, T, Lőrincz, I, Szebeni, A, Kecskeméti, V, Nánási, PP, Szentandrássy, N, Bárándi, L, Simkó, J, Horváth, B, Bányász, T, Lorincz, I, Kecskeméti, V, and Nánási, P P

Subjects
*ROSIGLITAZONE, *ACTION potentials, *HEART ventricles, *LABORATORY dogs, *ARRHYTHMIA, *HEART cells, *VOLTAGE-clamp techniques (Electrophysiology), *CARDIOVASCULAR diseases risk factors
Abstract

Background and Purpose: In 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 Approach: Standard microelectrode techniques, conventional whole cell patch clamp and action potential voltage clamp techniques were applied in enzymatically dispersed ventricular cells from dog hearts.Key Results: At concentrations ≥10 µM 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, concentration-dependently, under conventional voltage clamp conditions and altered their kinetic properties. The EC(50) value for this inhibition was 25.2 ± 2.7 µM for the transient outward K(+) current (I(to)), 72.3 ± 9.3 µM for the rapid delayed rectifier K(+) current (I(Kr)) and 82.5 ± 9.4 µM for the L-type Ca(2+) current (I(Ca) ) with Hill coefficients close to unity. The inward rectifier K(+) current (I(K1)) was not affected by rosiglitazone up to concentrations of 100 µM. Suppression of I(to), I(Kr), and I(Ca) was confirmed also under action potential voltage clamp conditions.Conclusions and Implications: Alterations 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. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

4. Mechanism of reverse rate-dependent action of cardioactive agents

Author

Gábor Harmati, Antonio Zaza, Norbert Szentandrássy, László Bárándi, László Virág, András Varró, Péter P. Nánási, Tamás Bányász, Ildikó Márton, Bányász, T, Bárándi, L, Harmati, G, Virág, L, Szentandrássy, N, Márton, I, Zaza, A, Varró, A, and Nánási, P

Subjects
Potassium Channel Blocker, Heart Ventricles, Guinea Pigs, Action Potentials, Rabbit, Drug action, Pharmacology, Biology, Klinikai orvostudományok, Biochemistry, Guinea Pig, Heart Ventricle, Guinea pig, Dogs, Heart Rate, Drug Discovery, Dog, Potassium Channel Blockers, medicine, Animals, Humans, Ventricular Function, Repolarization, Myocytes, Cardiac, Action Potential, Potassium Channels, Inwardly Rectifying, Animal, Organic Chemistry, Rate dependent, Potassium channel blocker, Orvostudományok, Membrane current, Rats, Anti-Arrhythmia Agent, cardiovascular system, Biophysics, Rat, Molecular Medicine, Action potential duration, Rabbits, Anti-Arrhythmia Agents, Microelectrodes, Human, medicine.drug
Abstract

Class 3 antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD), i.e. changes in APD are greater at longer than at shorter cycle lengths. In spite of the several theories developed to explain this reverse rate-dependency, its mechanism has been clarified only recently. The aim of the present study is to elucidate the mechanisms responsible for reverse rate-dependency in mammalian ventricular myocardium. Action potentials were recorded using conventional sharp microelectrodes from human, canine, rabbit, guinea pig, and rat ventricular myocardium in a rate-dependent manner. Rate-dependent drug-effects of various origin were studied using agents known to lengthen or shorten action potentials allowing thus to determine the drug-induced changes in APD as a function of the cycle length. Both drug-induced lengthening and shortening of action potentials displayed reverse rate-dependency in human, canine, and guinea pig preparations, but not in rabbit and rat myocardium. Similar results were obtained when repolarization was modified by injection of inward or outward current pulses in isolated canine cardiomyocytes. In contrast to reverse rate-dependence, drug-induced changes in APD well correlated with baseline APD values (i.e. that measured before the superfusion of drug or injection of current) in all of the preparations studied. Since the net membrane current (I(net)), determined from the action potential waveform at the middle of the plateau, was inversely proportional to APD, and consequently to cycle length, it is concluded that that reverse rate-dependency may simply reflect the inverse relationship linking I(net) to APD. In summary, reverse rate-dependency is an intrinsic property of drug action in the hearts of species showing positive APD - cycle length relationship, including humans. This implies that development of a pure K(+) channel blocking agent without reverse rate-dependent effects is not likely to be successful.

Published
2011

5. Reverse rate dependency is an intrinsic property of canine cardiac preparations

Author

Stefano Marangoni, Norbert Szentandrássy, László Bárándi, Péter P. Nánási, Antonio Zaza, László Virág, Balázs Horváth, János Magyar, Gábor Harmati, András Varró, Tamás Bányász, Bányász, T, Horváth, B, Virág, L, Bárándi, L, Szentandrássy, N, Harmati, G, Magyar, J, Marangoni, S, Zaza, A, Varró, A, Nánási, P, Élettani Intézet -- 10, ÁOK -- OEC, and Debreceni Egyetem

Subjects
Male, Time Factors, Physiology, Barium Compounds, Action Potentials, 030204 cardiovascular system & hematology, Veratrine, 0302 clinical medicine, BIO/09 - FISIOLOGIA, Myocyte, Myocytes, Cardiac, Rate dependency, Nicorandil, Sulfonamides, 0303 health sciences, Pulse (signal processing), musculoskeletal, neural, and ocular physiology, Cardiac Pacing, Artificial, Models, Cardiovascular, Orvostudományok, cardiovascular system, Action potential duration, Female, Cardiology and Cardiovascular Medicine, Anti-Arrhythmia Agents, medicine.drug, circulatory and respiratory physiology, medicine.medical_specialty, Heart Ventricles, Biophysics, Dofetilide, In Vitro Techniques, Klinikai orvostudományok, Purkinje Fibers, 03 medical and health sciences, Dogs, Chlorides, Physiology (medical), Internal medicine, Phenethylamines, medicine, Repolarization, Animals, Computer Simulation, 030304 developmental biology, business.industry, 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, Membrane current, rate-dependency, action potential, action potential duration, reverse rate dependence, ventricular repolarization, membrane current, dog myocytes, Endocrinology, Nonlinear Dynamics, business, 030217 neurology & neurosurgery
Abstract

AIMS: Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further elucidate the mechanisms responsible for reverse rate-dependent drug effects. METHODS AND RESULTS: Action potentials were recorded from multicellular canine ventricular preparations and isolated cardiomyocytes, at cycle lengths (CLs) varying from 0.3 to 5 s, using conventional sharp microelectrodes. APD was either modified by applying inward and outward current pulses, or by superfusion of agents known to lengthen and shorten APD. Net membrane current (I(m)) was calculated from action potential waveforms. The hypothesis that RRD may be implicit in the relationship between I(m) and APD was tested by numerical modelling. Both drug-induced lengthening (by veratrine, BAY-K 8644, dofetilide, and BaCl(2)) and shortening (by lidocaine and nicorandil) of action potentials displayed RRD, i.e. changes in APD were greater at longer than at shorter CL. A similar dependency of effect on CL was found when repolarization was modified by injection of inward or outward current pulses. I(m) measured at various points during repolarization was inversely proportional to APD and to CL. Model simulations showed that RRD is expected as a consequence of the non-linearity of the relationship between I(m) and APD. CONCLUSION: RRD of APD modulation is shared, although with differences in magnitude, by interventions of very different nature. RRD can be interpreted as a consequence of the relationship between I(m) and APD and, as such, is expected in all species having positive APD-CL relationship. This implies that the development of agents prolonging APD with direct rate dependency, or even completely devoid of RRD, may be difficult to achieve.

Published
2009

Catalog

Books, media, physical & digital resources
See catalog results