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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.
Dátum:	2008
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 DOI
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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)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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