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1.

001-es BibID:BIBFORM001011
Első szerző:Bányász Tamás (élettanász)
Cím:Action potencial clamp fingerprints of K+ currents in canine cardiomyocytes : their role in ventricular repolarization / Bányász T., Magyar J., Szentandrássy N., Horváth B., Birinyi P., Szentmiklósi J., Nánási P.
Dátum:2007
Megjegyzések:The aim of the present study was to give a parametric description of the most important K(+) currents flowing during canine ventricular action potential. METHODS: Inward rectifier K(+) current (I(K1)), rapid delayed rectifier K(+) current (I(Kr)), and transient outward K(+) current (I(to)) were dissected under action potential clamp conditions using BaCl(2), E-4031, and 4-aminopyridine, respectively. RESULTS: The maximum amplitude of I(to) was 3.0 +/- 0.23 pA/pF and its integral was 29.7 +/- 2.5 fC/pF. The current peaked 4.4 +/- 0.7 ms after the action potential upstroke and rapidly decayed to zero with a time constant of 7.4 +/- 0.6 ms. I(Kr) gradually increased during the plateau, peaked 7 ms before the time of maximum rate of repolarization (V(max)(-)) at -54.2 +/- 1.7 mV, had peak amplitude of 0.62 +/- 0.08 pA/pF, and integral of 57.6 +/- 6.7 fC/pF. I(K1) began to rise from -22.4 +/- 0.8 mV, peaked 1 ms after the time of V(max)(-) at -58.3 +/- 0.6 mV, had peak amplitude of 1.8 +/- 0.1 pA/pF, and integral of 61.6 +/- 6.2 fC/pF. Good correlation was observed between peak I(K1) and V(max)(-) (r = 0.93) but none between I(Kr) and V(max)(-). Neither I(K1) nor I(Kr) was frequency-dependent between 0.2 and 1.66 Hz. Congruently, I(Kr) failed to accumulate in canine myocytes at fast driving rates. CONCLUSION: Terminal repolarization is dominated by I(K1), but action potential duration is influenced by several ion currents simultaneously. As I(to) was not active during the plateau, and neither I(K1) nor I(Kr) was frequency-dependent, other currents must be responsible for the frequency dependence of action potential duration at normal and slow heart rates in canine ventricular cells.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Acta Physiologica (Oxford, England). - 190 : 3 (2007), p. 189-198. -
További szerzők:Magyar János (1961-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Horváth Balázs (1981-) (élettanász) Birinyi Péter (1981-) (élettanász) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Nánási Péter Pál (1956-) (élettanász)
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2.

001-es BibID:BIBFORM032923
035-os BibID:PMID:16086157
Első szerző:Birinyi Péter (élettanász)
Cím:Effects of SEA0400 and KB-R7943 on Na+/Ca2+ exchange current and L-type Ca2+ current in canine ventricular cardiomyocytes / Péter Birinyi, Károly Acsai, Tamás Bányász, András Tóth, Balázs Horváth, László Virág, Norbert Szentandrássy, János Magyar, András Varró, Ferenc Fülöp, Péter P. Nánási
Dátum:2005
ISSN:0028-1298
Megjegyzések:SEA0400 and KB-R7943 are compounds synthesised to block transsarcolemmal Na+/Ca2+ exchange current (INa/Ca); however, they Have also been shown to inhibit L-type Ca2+ current (ICa). The potential value of these compounds depends critically on their relative selectivity for INa/Ca over ICa. In the present work, therefore, the concentration-dependent effects of SEA0400 and KB-R7943 on INa/Ca and ICa were studied and compared in canine ventricular cardiomyocytes using the whole-cell configuration of the patch clamp technique. SEA0400 and KB-R7943 decreased INa/Ca in a concentration-dependent manner, having EC50 values of 111?43 nM and 3.35?0.82 mgrM, when suppressing inward currents, while the respective EC50 values were estimated at 108?18 nM and 4.74?0.69 mgrM in the case of outward current block. SEA0400 and KB-R7943 also blocked ICa, having comparable EC50 values (3.6 mgrM and 3.2 mgrM, respectively). At higher concentrations (10 mgrM) both drugs accelerated inactivation of ICa, retarded recovery from inactivation and shifted the voltage dependence of inactivation towards more negative voltages. The voltage dependence of activation was slightly modified by SEA0400, but not by KB-R7943. Based on the relatively good selectivity of submicromolar concentrations of SEA0400?but not KB-R7943?for INa/Ca over ICa, SEA0400 appears to be a suitable tool to study the role of INa/Ca in Ca2+ handling in canine cardiac cells. At concentrations higher than 1 mgrM, however, ICa is progressively suppressed by the compound.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
SEA0400
KB-R7943
Na+/Ca2+ exchanger
Ca2+ current
Cardiac cells
Dog
Voltage clamp
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives Of Pharmacology. - 372 : 1 (2005), p. 63-70. -
További szerzők:Acsai Károly Bányász Tamás (1960-) (élettanász) Tóth András Horváth Balázs (1981-) (élettanász) Virág László (élettanász Szeged) Szentandrássy Norbert (1976-) (élettanász) Magyar János (1961-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus) Fülöp Ferenc (Szeged) Nánási Péter Pál (1956-) (élettanász)
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3.

001-es BibID:BIBFORM004074
Első szerző:Birinyi Péter (élettanász)
Cím:The Na+/Ca2+ exchange blocker SEA0400 fails to enhance cytosolic Ca2+ transient and contractility in canine ventricular cardiomyocytes / Birinyi P., Tóth A., Jóna I., Acsai K., Almássy J., Nagy N., Prorok J., Gherasim I., Papp Z., Hertelendi Z., Szentandrássy N., Bányász T., Fülöp F., Papp J. G., Varró A., Nánási P. P., Magyar J.
Dátum:2008
Megjegyzések:Aims This study was designed to evaluate the effects of the Na+/Ca2+ exchange (NCX) inhibitor SEA0400 on Ca2+ handling in isolated canine ventricular myocytes. Methods and results Intracellular Ca2+ ([Ca2+](i)) transients, induced by either field stimulation or caffeine flush, were monitored using Ca2+ indicator dyes. [Ca2+](i)-dependent modulation of the inhibitory effect of SEA0400 on NCX was characterized by the changes in Ni2+-sensitive current in voltage-clamped myocytes. Sarcoplasmic reticulum (SR) Ca2+ release and uptake were studied in SIR membrane vesicles. Gating properties of single-ryanodine receptors were analysed in lipid bilayers. Ca2+ sensitivity of the contractile machinery was evaluated in chemically skinned myocytes. In myocytes paced at 1 Hz, neither diastolic [Ca2+](i) nor the amplitude of [Ca2+](i) transients was significantly altered by SEA0400 up to the concentration of 1 mu M, which was shown to inhibit the exchange current. The blocking effect of SEA0400 on NCX decreased with increasing [Ca2+](i), and it was more pronounced in reverse than in forward mode operation at every [Ca2+](i) examined. The rate of decay of the caffeine-induced [Ca2+](i) transients was decreased significantly by 1 mu M SEA0400; however, this effect was only a fraction of that observed with 10 mM NiCl2. Neither SR Ca2+ release and uptake nor cell shortening and Ca2+ sensitivity of the contractile proteins were influenced by SEA0400. Conclusion The lack of any major SEA0400-induced shift in Ca2+ transients or contractility of myocytes can well be explained by its limited inhibitory effect on NCX (further attenuated by elevated [Ca2+](i) levels) and a concomitant reduction in Ca2+ influx due to the predominantly reverse mode blockade of NCX and suppression of L-type Ca2+ current.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Cardiovascular Research. - 78 : 3 (2008), p. 476-484. -
További szerzők:Tóth András (farmakológus) Jóna István (1948-) (élettanász, fizikus) Acsai Károly Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító) Nagy Norbert (1977-) (kísérletes farmakológus) Prorok János Gherasim, Iuliana Papp Zoltán (1965-) (kardiológus, élettanász) Hertelendi Zita (1978-) (orvos) Szentandrássy Norbert (1976-) (élettanász) Bányász Tamás (1960-) (élettanász) Fülöp Ferenc Papp Gy. Julius (Szeged) Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász) Magyar János (1961-) (élettanász)
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4.

001-es BibID:BIBFORM036996
Első szerző:Gönczi Mónika (élettanász)
Cím:Age-dependent changes in ion channel mRNA expression in canine cardiac tissues / Gönczi Mónika, Birinyi Péter, Balázs Bernadett, Szentandrássy Norbert, Harmati Gábor, Könczei Zoltán, Csernoch László, Nánási Péter P.
Dátum:2012
Megjegyzések:The expression pattern of cardiac ion channels displays marked changes during ontogeny.This study was designed to follow the developmental changes in the expression of major ventricularand atrial ion channel proteins (including both pore forming and regulatory subunits) in canine cardiactissues at the mRNA level using competitive reverse transcription polymerase chain reaction. Therefore,the corresponding mRNA levels were compared in myocardial tissues excised from embryonic (25?60days of gestation) and adult (2?3 years old) canine hearts. Expression level of Kv4.3, Kv1.4, KChIP2,KvLQT1, and Cav3.2 mRNAs were higher in the adult than in the embryonic hearts, while expressionof Nav1.5 and minK mRNAs were higher in the embryonic than in the adult myocardium. No change inKir2.1, HERG, Kv1.5, and Cav1.2 mRNA was observed during ontogeny. Direction of the developmentalchange in the mRNA level, determined for any specific channel protein, was identical in the atrial andventricular samples. The age-dependent increase observed in the expression of Kv4.3, Kv1.4, KChIP2, andKvLQT1 is congruent with the greater repolarization reserve of the adult myocardium, associated withhigher densities of Ito and IKs. The results indicate that age-dependent changes in the expression patternof many ion channels are similar in canine and healthy human myocardium, therefore, canine cardiacmuscle can be considered as a good model of studying developmental changes in the human heart.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Developmental changes
Dog heart
Ion channels
mRNA expression
Regional differences
Molekuláris Medicina
Megjelenés:General physiology and biophysics. - 31 : 2 (2012), p. 153-162. -
További szerzők:Birinyi Péter (1981-) (élettanász) Balázs Bernadett Szentandrássy Norbert (1976-) (élettanász) Harmati Gábor (1983-) (élettanász) Könczei Zoltán Csernoch László (1961-) (élettanász) 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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5.

001-es BibID:BIBFORM020123
Első szerző:Horváth Balázs (élettanász)
Cím:Contribution of I-Ks to ventricular repolarization in canine myocytes / Balázs Horváth, János Magyar, Norbert Szentandrássy, Péter Birinyi, Péter P. Nánási, Tamás Bányász
Dátum:2006
ISSN:0031-6768
Megjegyzések:The role of the slow delayed rectifier K+ current (I-Ks) in cardiac repolarization seems to be largely influenced by the experimental conditions including the species and tissue studied. The aim of this study was to determine the contribution of I-Ks, to repolarization in canine ventricular myocytes by measuring the frequency dependent action potential lengthening effect of 10 mu M chromanol 293B using sharp microelectrodes. Pretreatment with isoproterenol (2 nM), E-4031 (1 mu M), and injection of inward current pulses were applied to modify action potential configuration. Chromanol alone caused moderate but statistically significant lengthening of action potentials at cycle lengths longer than 500 ms. The lengthening effect of chromanol, which was strongly enhanced in the presence of either isoproterenol or E-4031, was proportional to the amplitude of plateau, whereas poor correlation was found with action potential duration. Similar results were obtained when action potential configuration was modified by injection of depolarizing current pulses. Computer simulations revealed that activation of I-Ks is a sharp function of the plateau amplitude within the physiological range, while elongation of repolarization may enhance I-Ks only when it is excessive. It was concluded that the effect of I-Ks on ventricular repolarization critically depends on the level of action potential plateau; however, other factors, like action potential duration, cycle length, or suppression of other K+ currents can also influence its contribution.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Pflügers Archiv. - 452 : 6 (2006), p. 698-706. -
További szerzők:Magyar János (1961-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Birinyi Péter (1981-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Bányász Tamás (1960-) (élettanász)
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6.

001-es BibID:BIBFORM049664
Első szerző:Magyar János (élettanász)
Cím:SEA0400 Fails To Alter The Magnitude Of Intracellular Ca2+ Transients And Contractions In Guinea Pig Heart / János Magyar, Norbert Szentandrássy, Péter Birinyi, Attila Farkas, András Tóth, László Csernoch, András Varró, Péter P. Nánási
Dátum:2009
ISSN:0006-3495
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
Megjelenés:Biophysical Journal. - 96 : 3 (2009), p. 512a. -
További szerzők:Szentandrássy Norbert (1976-) (élettanász) Birinyi Péter (1981-) (élettanász) Farkas Attila (1961-) (farmakológus) Tóth András (farmakológus) Csernoch László (1961-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
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7.

001-es BibID:BIBFORM020122
Első szerző:Magyar János (élettanász)
Cím:L-364,373 fails to activate the slow delayed rectifier K+ current in canine ventricular cardiomyocytes / János Magyar, Balázs Horváth, Tamás Bányász, Norbert Szentandrássy, Péter Birinyi, András Varró, Zsolt Szakonyi, Ferenc Fülöp, Péter P. Nánási
Dátum:2006
ISSN:0028-1298
Megjegyzések:Activators of the slow delayed rectifier K+ current (I-Ks) are promising tools to suppress ventricular arrhythmias originating from prolongation of action potentials. A recently synthesized compound, L-364,373, was shown to activate I-Ks in ventricular cells isolated from guinea pigs and rabbits. Due to the interspecies differences known to exist in the properties of the delayed rectifier K+ currents, the effect of L-364,373 on I-Ks was studied and compared with that of another I-Ks activator mefenamic acid in canine ventricular myocytes. Mefenamic acid (100 mu M) significantly increased the amplitude of the fully activated I-Ks current, as well as the I-Ks current tails, by shifting the voltage dependence of its activation towards negative voltages and increased the time constant for deactivation. In contrast, L-364,373, up to concentrations of 3 mu M, failed to augment I-Ks at any membrane potential studied, but slightly increased the time constant of deactivation. It is concluded that human studies are required to evaluate the therapeutically beneficial effects of I-Ks activators. Rodent cardiac tissues are not suitable for this purpose.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 373 : 1 (2006), p. 85-89. -
További szerzők:Horváth Balázs (1981-) (élettanász) Bányász Tamás (1960-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Birinyi Péter (1981-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus) Szakonyi Zsolt Fülöp Ferenc Nánási Péter Pál (1956-) (élettanász)
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8.

001-es BibID:BIBFORM009091
Első szerző:Szabó Adrienn (egyetemi tanársegéd, fogszakorvos)
Cím:Effects of ropivacaine on action potential configuration and ion currents in isolated canine ventricular cardiomyocytes / Szabo, A., Szentandrassy, N., Birinyi, P., Horvath, B., Szabo, G., Banyasz, T., Marton, I., Magyar, J., Nanasi, P. P.
Dátum:2008
ISSN:1528-1175 (Electronic)
Megjegyzések:Despite the widespread clinical application of ropivacaine, there is little information on the cellular cardiac effects of the drug. In the current study, therefore, the concentration-dependent effects of ropivacaine on action potential morphology and the underlying ion currents were studied and compared with those of bupivacaine in isolated canine ventricular cardiomyocytes. METHODS: Action potentials were recorded from the enzymatically dispersed cells using sharp microelectrodes. Conventional patch clamp and action potential voltage clamp arrangements were used to study the effects of ropivacaine on transmembrane ion currents. RESULTS: Ropivacaine induced concentration- and frequency-dependent changes in action potential configuration, including shortening of the action potentials, reduction of their amplitude and maximum velocity of depolarization, suppression of early repolarization, and depression of plateau. Reduction in maximum velocity of depolarization was characterized with an EC50 value of 81 +/- 7 microm at 1 Hz. Qualitatively similar results were obtained with bupivacaine (EC50 = 47 +/- 3 microm). Under voltage clamp conditions, a variety of ion currents were blocked by ropivacaine: L-type calcium current (EC50 = 263 +/- 67 microm), transient outward current (EC50 = 384 +/- 75 microm), inward rectifier potassium current (EC50 = 372 +/- 35 microm), rapid delayed rectifier potassium current (EC50 = 303 +/- 47 microm), and slow delayed rectifier potassium current (EC50 = 106 +/- 18 microm). CONCLUSIONS: Ropivacaine, similarly to bupivacaine, can modify cardiac action potentials and the underlying ion currents at concentrations higher than the usual therapeutic range. However, in cases of overdose, cardiac complications may be anticipated both during and after anesthesia due to the blockade of various ion currents.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Action Potentials
Amides
Animals
Dogs
Dose-Response Relationship, Drug
Female
Heart Ventricles
Ion Channels
Ion Transport
Male
Myocytes, Cardiac
Ventricular Function
Megjelenés:Anesthesiology. - 108 : 4 (2008), p. 693-702. -
További szerzők:Szentandrássy Norbert (1976-) (élettanász) Birinyi Péter (1981-) (élettanász) Horváth Balázs (1981-) (élettanász) Szabó Gergely (1980-) (élettanász) Bányász Tamás (1960-) (élettanász) Márton Ildikó (1954-) (fogszakorvos) Magyar János (1961-) (élettanász) Nánási Péter Pál (1956-) (élettanász)
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9.

001-es BibID:BIBFORM001022
Első szerző:Szabó Adrienn (egyetemi tanársegéd, fogszakorvos)
Cím:Effects of articaine on action potential characteristics and the underlying ion currents in canine ventricular myocytes / Szabó A., Szentandrássy N., Birinyi P., Horváth B., Szabó G., Bányász T., Márton I., Nánási P.P., Magyar J.
Dátum:2007
Megjegyzések:In spite of its widespread clinical application, there is little information on the cellular cardiac effects of articaine. In the present study, the concentration-dependent effects of articaine on action potential morphology and the underlying ion currents were studied in isolated canine ventricular cardiomyocytes. METHODS: Action potentials were recorded from the enzymatically dispersed myocytes using sharp microelectrodes (16 cells from 3 dogs). Conventional patch clamp and action potential voltage clamp arrangements were used to study the effects of articaine on transmembrane ion currents (37 cells from 14 dogs). RESULTS: Articaine-induced concentration-dependent changes in action potential configuration including shortening of the action potentials, reduction of their amplitude and maximum velocity of depolarization (V(max)), suppression of early repolarization and depression of plateau. The EC50 value obtained for the V(max) block was 162 (sd 30) microM. Both the reduction of V(max) and action potential shortening were frequency dependent: the former was more prominent at shorter, while the latter at longer pacing cycle lengths. A rate dependent V(max) block, having rapid offset kinetics [tau = 91 (20) ms], was observed in addition to tonic block. Under voltage clamp conditions, a variety of ion currents were blocked by articaine: I(Ca) [EC50 = 471 (75) microM], I(to) [EC50 = 365 (62) microM], I(K1) [EC50 = 372 (46) microM], I(Kr) [EC50 = 278 (79) microM], and I(Ks) [EC50 = 326 (65) microM]. Hill coefficients were close to unity indicating a single binding site for articaine, except for I(K1). CONCLUSIONS: Articaine can modify cardiac action potentials and ion currents at concentrations higher than the therapeutic range which can be achieved only by accidental venous injection. Since its suppressive effects on the inward and outward currents are relatively well balanced, the articaine-induced changes in action potential morphology may be moderate even in the case of overdose.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:British Journal of Anaesthesia. - 99 : 5 (2007), p. 726-733. -
További szerzők:Szentandrássy Norbert (1976-) (élettanász) Birinyi Péter (1981-) (élettanász) Horváth Balázs (1981-) (élettanász) Szabó Gergely (1980-) (élettanász) Bányász Tamás (1960-) (élettanász) Márton Ildikó (1954-) (fogszakorvos) Nánási Péter Pál (1956-) (élettanász) Magyar János (1961-) (élettanász)
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10.

001-es BibID:BIBFORM004111
Első szerző:Szentandrássy Norbert (élettanász)
Cím:SEA0400 fails to alter the magnitude of intracellular Ca2+ transients and contractions in Langendorff-perfused guinea pig hearts / Szentandrássy N., Birinyi P., Szigeti Gy., Farkas A., Magyar J., Tóth A., Csernoch L., Varró A., Nánási P.P.
Dátum:2008
Megjegyzések:SEA0400 is a recently developed inhibitor of the Na+/Ca2+ exchanger (NCX) shown to suppress both forward and reverse mode operation of NCX. Present experiments were designed to study the effect of partial blockade of NCX on Ca handling and contractility in Langendorff-perfused guinea pig hearts loaded with the fluorescent Ca-sensitive dye fura-2. Left ventricular pressure and intracellular calcium concentration ([Ca2+]i) were synchronously recorded before and after cumulative superfusion with 0.3 and 1 muM SEA0400. SEA0400 caused no significant change in the systolic and diastolic values of left ventricular pressure and [Ca2+]i. Accordingly, pulse pressure and amplitude of the [Ca2+]i transient also remained unchanged in the presence of SEA0400. SEA0400 had no influence either on the time required to reach peak values of pressure and [Ca2+)]i or on half relaxation time. On the other hand, both 0.3 and 1 microM SEA0400 significantly increased the decay time constant of [Ca2+]i transients, obtained by fitting its descending limb between 30% and 90% of relaxation, from 127 +/- 7 to 165 +/- 7 and 177 +/- 14 ms, respectively (P < 0.05, n=6). In contrast to the guinea pig hearts, rat hearts responded to SEA0400 treatment with increased [Ca2+]i transients and contractility. These interspecies differences observed in the effect of SEA0400 can be explained by the known differences in calcium handling between the two species.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Naunyn-Schmiedeberg's Archives of Pharmacology. - 378 : 1 (2008), p. 65-71. -
További szerzők:Birinyi Péter (1981-) (élettanász) Szigeti Gyula (1969-) (élettanász, elektrofiziológus) Farkas Attila (1961-) (farmakológus) Magyar János (1961-) (élettanász) Tóth András (farmakológus) Csernoch László (1961-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
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