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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
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
Na+/Ca2+ exchanger
Ca2+ current
Cardiac cells
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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001-es BibID:BIBFORM004076
Első szerző:Farkas S. Attila
Cím:Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart / Farkas A. S., Acsai K., Nagy N., Tóth A., Fülöp F., Seprényi G., Birinyi P., Nánási P. P., Forster T., Csanády M., Papp J. G., Varró A., Farkas A.
Megjegyzések:The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts. EXPERIMENTAL APPROACH: The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry. KEY RESULTS: SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities. CONCLUSIONS AND IMPLICATIONS: NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:British Journal of Pharmacology. - 154 : 1 (2008), p. 93-104. -
További szerzők:Acsai Károly Nagy N. (Szeged) Tóth A. Fülöp Ferenc (Szeged) Seprényi G. Birinyi Péter (1981-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Forster Tamás Csanády Miklós (Szeged) Papp J. G. Varró András (1954-) (farmakológus, klinikai farmakológus) Farkas A. (Szeged)
Internet cím:elektronikus változat
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