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1.

001-es BibID:BIBFORM030249
035-os BibID:WOS:000187895800005
Első szerző:Bányász Tamás (élettanász)
Cím:Profile of I(Ks) during the action potential questions the therapeutic value of I(Ks) blockade / Tamás Bányász, Roland Koncz, László Fülöp, Norbert Szentandrássy, János Magyar, Péter P. Nánási
Dátum:2004
ISSN:0929-8673
Megjegyzések:The goal of this paper is two fold. First, we attempt to review the reports available on the role Of I-Ks in myocardial repolarization. Based on theoretical considerations and experimental results, it seems reasonable to assume that I-Ks blockade will lengthen the action potential. However, results obtained with I-Ks blockers, like chromanol 293B or L-735,821, are conflicting, since from slight lengthening to marked prolongation of action potentials were equally obtained. Although these contradictory results were explained by interspecies or regional differences, the role Of I-Ks in repolarization is a matter of growing dispute. In the second part of this study, we simulated the performance Of I-Ks during cardiac action potentials. We compared the profile of the predicted current in three mathematical models in order to determine the relative role of the current in repolarization. We studied the effect of the cycle length, action potential duration and height of the plateau on the profile Of I-Ks in epicardiac, endocardiac and midmyocardiac ventricular action potentials. The results indicate that the height of the plateau is the most important parameter to control activation Of I-Ks in cardiac tissues, and accordingly, the interspecies and regional differences observed in the efficacy Of I-Ks blockers are likely due to the known differences in action potential morphology. We conclude also that I-Ks blockade may have unpredictable effects on the length of the action potential in a diseased heart, questioning the possible therapeutic value of drugs blocking I-Ks.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Current Medicinal Chemistry. - 11 : 1 (2004), p. 45-60. -
További szerzők:Koncz Roland Fülöp László (1976-) (kardiológus) Szentandrássy Norbert (1976-) (élettanász) Magyar János (1961-) (élettanász) Nánási Péter Pál (1956-) (élettanász)
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2.

001-es BibID:BIBFORM020231
035-os BibID:WOS:000294414700009
Első szerző:Bányász Tamás (élettanász)
Cím:Cardiac calmodulin kinase : a potential target for drug design / Banyasz T., Szentandrassy N., Toth A., Nanasi P. P., Magyar J., Chen-Izu Y.
Dátum:2011
ISSN:0929-8673
Megjegyzések:Therapeutic strategy for cardiac arrhythmias has undergone a remarkable change during the last decades. Currently implantable cardioverter defibrillator therapy is considered to be the most effective therapeutic method to treat malignant arrhythmias. Some even argue that there is no room for antiarrhythmic drug therapy in the age of implantable cardioverter defibrillators. However, in clinical practice, antiarrhythmic drug therapies are frequently needed, because implantable cardioverter defibrillators are not effective in certain types of arrhythmias (i.e. premature ventricular beats or atrial fibrillation). Furthermore, given the staggering cost of device therapy, it is economically imperative to develop alternative effective treatments. Cardiac ion channels are the target of a number of current treatment strategies, but therapies based on ion channel blockers only resulted in moderate success. Furthermore, these drugs are associated with an increased risk of proarrhythmia, systemic toxicity, and increased defibrillation threshold. In many cases, certain ion channel blockers were found to increase mortality. Other drug classes such as beta-blockers, angiotensin-converting enzyme inhibitors, aldosterone antagonists, and statins appear to have proven efficacy for reducing cardiac mortality. These facts forced researchers to shift the focus of their research to molecular targets that act upstream of ion channels. One of these potential targets is calcium/calmodulin-dependent kinase II (CaMKII). Several lines of evidence converge to suggest that CaMKII inhibition may provide an effective treatment strategy for heart diseases. (1) Recent studies have elucidated that CaMKII plays a key role in modulating cardiac function and regulating hypertrophy development. (2) CaMKII activity has been found elevated in the failing hearts from human patients and animal models. (3) Inhibition of CaMKII activity has been shown to mitigate hypertrophy, prevent functional remodeling and reduce arrhythmogenic activity. In this review, we will discuss the structural and functional properties of CaMKII, the modes of its activation and the functional consequences of CaMKII activity on ion channels.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3707-3713. -
További szerzők:Szentandrássy Norbert (1976-) (élettanász) Tóth András (farmakológus) Nánási Péter Pál (1956-) (élettanász) Magyar János (1961-) (élettanász) Chen-Izu, Ye
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3.

001-es BibID:BIBFORM024502
035-os BibID:(WoS)000294414700002 (Scopus)80052005781
Első szerző:Bányász Tamás (élettanász)
Cím:Mechanism of reverse rate-dependent action of cardioactive agents / Tamás Bányász, László Bárándi, Gábor Harmati, László Virág, Norbert Szentandrássy, Ildikó Márton, Antonio Zaza, András Varró, Péter P. Nánási
Dátum:2011
ISSN:0929-8673 1875-533X
Megjegyzések: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.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
antiarrhythmiás szerek
APD
Molekuláris Medicina
egyetemen (Magyarországon) készült közlemény
Megjelenés:Current medicinal chemistry. - 18 : 24 (2011), p. 3597-3606. -
További szerzők:Bárándi László (1984-) (élettanász) Harmati Gábor (1983-) (élettanász) Virág László (élettanász Szeged) Szentandrássy Norbert (1976-) (élettanász) Márton Ildikó (1954-) (fogszakorvos) Zaza, Antonio Varró András (1954-) (farmakológus, klinikai farmakológus) 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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4.

001-es BibID:BIBFORM049492
Első szerző:Hegyi Bence (élettanász)
Cím:Selectivity problems with drugs acting on cardiac Na+ and Ca2+ channels / Bence Hegyi, István Komáromi, Péter P. Nánási, Norbert Szentandrássy
Dátum:2013
ISSN:0929-8673
Megjegyzések:With the increase of our knowledge on cardioactive agents it comes more and more clear that practically none of the currently used compounds shows absolute selectivity to one or another ion channel type. This is particularly true for Na(+) and Ca(2+) channel modulators, which are widely applied in the clinical practice and biomedical research. The best example might be probably the marine guanidine poison tetrodotoxin, which has long been considered as a selective Na(+) channel blocker, while recently it turned out to effectively inhibit cardiac Ca(2+) currents as well. In the present study the cross actions observed between the effects of various blockers of Na(+) channels (such as toxin inhibitors, class I antiarrhythmics and local anesthetics) and Ca(2+) channels (like phenylalkylamines, dihydropyridine compounds, diltiazem and mibefradil) are overviewed in light of the known details of the respective channel structures. Similarly, activators of Na(+) channels, including veratridine and batrachotoxin, are also compared. The binding of tetrodotoxin and saxitoxin to Cav1.2 and Nav1.5 channel proteins is presented by construction of theoretical models to reveal common structures in their pore forming regions to explain cross reactions. Since these four domain channels can be traced back to a common ancestor, a close similarity in their structure can well be demonstrated. Thus, the poor selectivity of agents acting on cardiac Na(+) and Ca(2+) channels is a consequence of evolution. As a conclusion, since the limited selectivity is an intrinsic property of drug receptors, it has to be taken into account when designing new cardioactive compounds for either medical therapy or experimental research in the future.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Na+ channels
Ca2+ channels
ion selectivity
cardioactive drugs
channel structures
tetrodotoxin
Doktori iskola
Megjelenés:Current Medicinal Chemistry. - 20 : 20 (2013), p. 2552-2571. -
További szerzők:Komáromi István (1957-) (vegyész, molekuláris biológus, biokémikus) Nánási Péter Pál (1956-) (élettanász) Szentandrássy Norbert (1976-) (élettanász)
Pályázati támogatás:TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
Élettan Kutatócsoport
K100151
OTKA
PD101171
OTKA
K101196
OTKA
CNK-77855
OTKA
TÁMOP-4.2.2/B-10/1-2010-0024
TÁMOP
Molekuláris Orvostudomány Doktori Iskola
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DOI
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5.

001-es BibID:BIBFORM020232
035-os BibID:WOS:000294414700010
Első szerző:Magyar János (élettanász)
Cím:Long term regulation of cardiac L-type calcium channel by small G proteins / Magyar J., Jenes A., Kistamas K., Ruzsnavszky F., Nanasi P. P., Satin J., Szentandrassy N., Banyasz T.
Dátum:2011
ISSN:0929-8673
Megjegyzések:Calcium ions are crucial elements of excitation-contraction coupling in cardiac myocytes. The intracellular Ca(2+) concentration changes continously during the cardiac cycle, but the Ca(2+) entering to the cell serves as an intracellular second messenger, as well. The Ca(2+) as a second messenger influences the activity of many intracellular signalling pathways and regulates gene expression. In cardiac myocytes the major pathway for Ca(2+) entry into cells is L-type calcium channel (LTCC). The precise control of LTCC function is essential for maintaining the calcium homeostasis of cardiac myocytes. Dysregulation of LTCC may result in different diseases like cardiac hypertrophy, arrhytmias, heart failure. The physiological and pathological structural changes in the heart are induced in part by small G proteins. These proteins are involved in wide spectrum of cell biological functions including protein transport, regulation of cell proliferation, migration, apoptosis, and cytoskeletal rearrangement. Understanding the crosstalk between small G proteins and LTCC may help to understand the pathomechanism of different cardiac diseases and to develop a new generation of genetically-encoded Ca(2+) channel inhibitors.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Molekuláris Medicina
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3714-3719. -
További szerzők:Jenes Ágnes (1980-) (élettanász) Kistamás Kornél (1986-) (biológus) Ruzsnavszky Ferenc (1984-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Satin, Jonathan Szentandrássy Norbert (1976-) (élettanász) Bányász Tamás (1960-) (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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6.

001-es BibID:BIBFORM020356
Első szerző:Nagy N. (Szeged)
Cím:Role of Ca(2)+-sensitive K+ currents in controlling ventricular repolarization : possible implications for future antiarrhytmic drug therapy / Nagy N., Marton Z., Kiss L., Varro A., Nanasi P. P., Toth A.
Dátum:2011
ISSN:1875-533X (Electronic)
Megjegyzések:Normal heart function and repolarization of the cardiac action potential (AP) is to a high extent subjective to synchronized activity of sarcolemmal K(+) channels, expressed in both ventricular and atrial myocardium, largely contributing to regulation of the resting potential, the pacemaker activity, and the shape and duration of the AP. Clinical observations and experimental studies in cardiomyocytes and multicellular preparations provided firm evidence for the sensitivity of some major outward K+ currents and the corresponding ion channels to shifts in intracellular Ca(2+) concentration ([Ca(2+)](i)). Direct regulation via interaction between [Ca(2+ )](i) and the channel protein or indirect modulation via Ca(2+ ) signaling pathways of these currents have strong implications to mechanical and electrical performance of the heart, and its physiological adaptation to altered load. It may also lead to severe cardiac dysfunction, if [Ca(2+ )](i) handling is disturbed in a variety of pathological conditions. In this review we attempt to summarize the present state of the topic on two ubiquitous repolarizing K(+) currents (I(to1) and I(K1)) with documented Ca(2+)-sensitivity and critical significance in cellular antiarrhythmic defense, to highlight fields where clue data are missing, and discuss the apparently unsolved "mystery" of the cardiac small conductance Ca(2+ )-activated K(+ ) (SK) channels. We have collected the available information on the known novel, although usually still not enough selective inhibitors and activators of these currents justifying the need for more selective ones. Finally, we emphasize a few related therapeutical perspectives to be considered for future experimental research and particularly in pharmaceutical development.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3622-3639. -
További szerzők:Marton Z. Kiss L. Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász) Tóth András (farmakológus)
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7.

001-es BibID:BIBFORM030213
035-os BibID:WOS:000294414700001
Első szerző:Nánási Péter Pál (élettanász)
Cím:Hot topic : hot topics in cellular cardiac electrophysiology with potential impact on future drug design / Péter P. Nánási, Valéria Kecskeméti
Dátum:2011
ISSN:0929-8673
Tárgyszavak:Orvostudományok Elméleti orvostudományok szerkesztőségi anyag
egyetemen (Magyarországon) készült közlemény
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3595-3596. -
További szerzők:Kecskeméti Valéria
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8.

001-es BibID:BIBFORM030332
035-os BibID:WOS:000080469500003
Első szerző:Pacher Pál
Cím:Speculations on difference between tricyclic and selective serotonin reuptake inhibitor antidepressants on their cardiac effects : Is there any? / Pal Pacher, Zoltan Ungvari, Peter P. Nanasi, Susanna Furst, Valeria Kecskemeti
Dátum:1999
ISSN:0929-8673
Megjegyzések:The cardiovascular effects and toxicity of tricyclic antidepressants (TCAs) have been well documented in medical literature. The most common manifestation of such effects is slowing of intraventricular conduction, manifested by prolonged PR, QRS and QT intervals on the standard electrocardiogram (ECG) and postural hypotension. In contrast to TCAs; selective serotonin reuptake inhibitors (SSRIs), including fluoxetine and citalopram, are considered to cause less effect on cardiac impulse conduction. In addition, these compounds induced significantly less anticholinergic, antihistaminergic and cardiotoxic side-effects than TCAs. However, there is an increasing number of case reports on dysrhythmias, like atrial fibrillation or bradycardia and syncope associated with fluoxetine and another SSRI treatment and overdose. Although such reports have not been common, they do raise concerns. In cardiac tissues isolated from canine, rabbit, rat and guinea pig hearts we have found that fluoxetine and citalopram inhibited cardiac Na+ and Ca2+ channels. These direct cardiac electrophysiological effects were similar to those of observed for tricyclic antidepressants clomipramine and imipramine. The inhibition of cardiac Ca2+ and Na+ channels by fluoxetine may explain most cardiac side-effects observed occasionally with the drug and mild but significant bradycardia reported during chronic treatment. Our results suggest that fluoxetine and citalopram may have antiarrhythmic (class I + IV type), as well as proarrhythmic properties (due to impairment of atrioventricular or intraventricular conduction and shortening of repolarization). Taking all these into consideration, in depressed patients having also severe cardiac disorders, ECG control may be suggested during fluoxetine and probable another SSRI therapy. The primary goal of this review is to compare these direct cardiac effects of fluoxetine and citalopram to those of previously reported for TCAs. This paper also summarizes the recently observed effects of fluoxetine apparently not related to the blockage of 5-HT transporter based on literature.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Current Medicinal Chemistry. - 6 : 6 (1999), p. 469-480. -
További szerzők:Ungvári Zoltán Nánási Péter Pál (1956-) (élettanász) Furst, Susanna Kecskeméti Valéria
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9.

001-es BibID:BIBFORM020359
Első szerző:Szabó Gergely (élettanász)
Cím:Enhanced repolarization capacity : new potential antiarrhythmic strategy based on hERG channel activation / Szabo G., Farkas V., Grunnet M., Mohacsi A., Nanasi P. P.
Dátum:2011
ISSN:1875-533X
Megjegyzések:The delayed rectifier potassium current (I(K)) is the major outward current responsible for ventricular repolarization in cardiac tissues. Based on kinetic properties and drug sensitivity it is composed of a slow (I(Ks)) and a rapid (I(Kr)) component, the latter is mediated by hERG channels. Suppression of IKr is the common mechanism of action of all class III antiarrhythmics, causing prolongation of the refractory period. However, lengthening of repolarization - either by a pathological factor or due to a pharmacological intervention - threatens with an increased risk of EAD generation and the concomitant sudden cardiac death. Therefore, a new potential anti-arrhythmic strategy, based on augmentation of the repolarization reserve, has been emerged. Recently a new class of compounds has been introduced as activators of the hERG channel. In this article we systematically review the chemical structures found to enhance IKr. Since the majority of previous experiments were performed in expression systems or in rodent cardiac preparations (neither is relevant to the human heart), in the second part of this article we present some results obtained with NS1643, the best examined hERG activator, in canine ventricular cardiomyocytes. This preparation is believed to have electrophysiological parameters most resembling those of human. NS1643 shortened the duration of canine ventricular action potential and was shown to interact with several transmembrane ion currents, including I(Ca), I(Kr), I(Ks), and I(to). However, the action potential shortening effect of NS1643 is likely related to inhibition of ICa, in addition to the enhancement of IKr. Although the multiple ion channel activity of NS1643 may carry proarrhythmic risk, the rationale of antiarrhythmic strategy based on I(Kr) activation is not questioned.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Molekuláris Medicina
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3607-3621. -
További szerzők:Farkas Viktória Grunnet, Morten Mohácsi A. 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
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:

10.

001-es BibID:BIBFORM037322
035-os BibID:WOS:000294414700011
Első szerző:Szebeni Andrea
Cím:Can the electrophysiological action of rosiglitazone explain its cardiac side effects? / A. Szebeni, N. Szentandrássy, P. Pacher, J. Simkó, P. P. Nánási, V. Kecskeméti
Dátum:2011
ISSN:0929-8673
Megjegyzések:Recent large clinical trials found an association between the antidiabetic drug rosiglitazone therapy and increased risk of cardiovascular adverse events. The aim of this report is to elucidate the cardiac electrophysiological properties of rosiglitazone (R) on isolated rat and murine ventricular papillary muscle cells and canine ventricular myocytes using conventional microelectrode, whole cellvoltage clamp, and action potential (AP) voltage clamp techniques.In histidine-decarboxylase knockout mice as well as in their wild types R (1-30 ?M) shortened AP duration at 90% level of repolarization (APD90) and increased the AP amplitude (APA) in a concentration-dependent manner. In rat ventricular papillary muscle cells R (1-30?M) caused a significant reduction of APA and maximum velocity of depolarization (Vmax) which was accompanied by lengthening of APD90.In single canine ventricular myocytes at concentrations ?10 ?M R decreased the amplitude of phase-1 repolarization, the plateau potential and reduced Vmax. R suppressed several ion currents in a concentration-dependent manner under voltage clamp conditions. The EC50value for this inhibition was 25.2?2.7 ?M for the transient outward K+ current (Ito), 72.3?9.3 ?M for the rapid delayed rectifier K+ current (IKr), and 82.5?9.4 ?M for the L-type Ca2+ current (ICa) with Hill coefficients close to unity. The inward rectifier K+ current (IK1) was not affected by R up to concentrations of 100 ?M. Suppression of Ito, IKr, and ICa has been confirmed under action potential voltage clamp conditions as well.The observed alterations in the AP morphology and densities of ion currents may predict serious proarrhythmic risk in case of intoxicationwith R as a consequence of overdose or decreased elimination of the drug, particularly in patients having multiple cardiovascular risk factors, such as elderly diabetic patients.
Tárgyszavak:Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban
antidiabetic agents
rosiglitazone
action potential
ion currents
egyetemen (Magyarországon) készült közlemény
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3720-3728. -
További szerzők:Szentandrássy Norbert (1976-) (élettanász) Pacher Pál Simkó József (1974-) (belgyógyász, kardiológus) Nánási Péter Pál (1956-) (élettanász) Kecskeméti Valéria
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DOI
Borító:

11.

001-es BibID:BIBFORM034919
035-os BibID:PMID:21774755 WOS:000294414700012
Első szerző:Szentandrássy Norbert (élettanász)
Cím:Modified cAMP derivatives : powerful tools in heart research / N. Szentandrássy, G. Harmati, V. Farkas, B. Horváth, B. Hegyi, J. Magyar, G. Szénási, I. Márton, P. P. Nánási
Dátum:2011
ISSN:0929-8673
Megjegyzések:Receptor-mediated changes in intracellular cyclic AMP concentration play critical role in the autonomic control of the heart, including regulation of a variety of ion channels via mechanisms involving protein kinase A, EPAC, or direct actions on cyclic nucleotide gated ion channels. In case of any ion channel, the actual signal transduction cascade can be identified by using properly modified cAMP derivatives with altered binding and activating properties. In this study we focus to structural modifications of cAMP resulting in specific activator and blocking effects on PKA or EPAC. Involvement of the cAMP-dependent signal transduction pathway in controlling rapid delayed rectifier K(+ ) current was studied in canine ventricular myocytes using these specific cAMP analogues. Adrenergic stimulation increased the density of I(Kr) in canine ventricular cells, which effect was mediated by a PKA-dependent but EPAC-independent pathway. It was also shown that intracellular application of large concentrations of cAMP failed to fully activate PKA comparing to the effect of isoproterenol, forskolin, or PDE-resistant cAMP derivatives. This difference was fully abolished following inhibition of phosphodiesterase by IBMX. These results are in line with the concept of compartmentalized release, action, and degradation of cAMP within signalosomes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Adrenergic stimulation
cAMP analogues
dog myocytes
EPAC
Molekuláris Medicina
intracellular compartmentalization
phosphodiesterase
protein kinase A
rapid delayed rectifier K+ current
cyclic nucleotide
modified cAMP derivatives
egyetemen (Magyarországon) készült közlemény
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3729-3736. -
További szerzők:Harmati Gábor (1983-) (élettanász) Farkas Viktória Horváth Balázs (1981-) (élettanász) Hegyi Bence (1987-) (élettanász) Magyar János (1961-) (élettanász) Szénási Gábor Márton Ildikó (1954-) (fogszakorvos) 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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DOI
Intézményi repozitóriumban (DEA) tárolt változat
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12.

001-es BibID:BIBFORM017197
Első szerző:Szentandrássy Norbert (élettanász)
Cím:Powerful technique to test selectivity of agents acting on cardiac ion channels : the action potential voltage-clamp / Norbert Szentandrássy, Dénes Nagy, Ferenc Ruzsnavszky, Gábor Harmati, Tamás Bányász, János Magyar, A. József Szentmiklósi, Péter P. Nánási
Dátum:2011
ISSN:0929-8673
Megjegyzések:Action potential voltage-clamp (APVC) is a technique to visualize the profile of various currents during the cardiacaction potential. This review summarizes potential applications and limitations of APVC, the properties of the mostimportant ion currents in nodal, atrial, and ventricular cardiomyocytes. Accordingly, the profiles ("fingerprints") of themajor ion currents in canine ventricular myocytes, i.e. in cells of a species having action potential morphology and setof underlying ion currents very similar to those found in the human heart, are discussed in details. The degree ofselectivity of various compounds, which is known to be a critical property of drugs used in APVC experiments, isoverviewed. Thus the specificity of agents known to block sodium (tetrodotoxin, saxitoxin), potassium (chromanol293B, HMR 1556, E-4031, dofetilide, sotalol, 4-aminopyridine, BaCl2), calcium (nifedipine, nisolpidine, nicardipine,diltiazem, verapamil, gallopamil), and chloride (anthracene-9-carboxylic acid, DIDS) channels, the inhibitor of thesodium-calcium exchanger (SEA0400), and the activator of sodium current (veratridine) are accordingly discussed.Based on a theory explaining how calcium current inhibitors block calcium channels, the structural comparison of thestudied substances usually confirmed the results of the literature. Using these predictions, a hypothetical super-selectivecalcium channel inhibitor structure was designed. APVC is a valuable tool not only for studying the selectivity of theknown ion channel blockers, but is also suitable for safety studies to exclude cardiac ion channel actions of any agentunder development.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
action potential
action potential voltage-clamp
Molekuláris Medicina
calcium channel
chemical structure
ion current
ion channel blocker
Molekuláris Medicina
selective calcium channel blocker
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3737-3756. -
További szerzők:Nagy Dénes (1984-) (vegyész) Ruzsnavszky Ferenc (1984-) (élettanász) Harmati Gábor (1983-) (élettanász) Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:K 73160
OTKA
CNK 77855
OTKA
K 68457
OTKA
TáMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
A feszültségfüggő K-csatornák szerepe excitábilis sejtekben
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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