Effect of sphingosine-1-phosphate on L-type calcium current and Ca2+ transient in rat ventricular myocytes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16370%2F16%3A43874428" target="_blank" >RIV/62157124:16370/16:43874428 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s11010-016-2752-8" target="_blank" >http://dx.doi.org/10.1007/s11010-016-2752-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s11010-016-2752-8" target="_blank" >10.1007/s11010-016-2752-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of sphingosine-1-phosphate on L-type calcium current and Ca2+ transient in rat ventricular myocytes

Popis výsledku v původním jazyce

Modulation of Ca2+ homoeostasis in cardiac myocytes plays a major role in beat-to-beat regulation of heart function. Previous studies suggest that sphingosine-1-phosphate (S1P), a biologically active sphingomyelin metabolite, regulates Ca2+ handling in cardiac myocytes, but the underlying mechanism is unclear. In the present study, we tested the hypothesis that S1P-induced functional alteration of intracellular Ca2+ handling includes the L-type calcium channel current (I-Ca,I-L) via a signalling pathway involving P21-activated kinase 1 (Pak1). Our results show that, in rat ventricular myocytes, S1P (100 nM) does not affect the basal activity of I-Ca,I-L but is able to partially reverse the effect of the beta-adrenergic agonist Isoproterenol (ISO, 100 nM) on I-Ca,I-L. S1P (25 nM) also significantly prevents ISO (5 nM)-induced Ca2+ waves and diastolic Ca2+ release in these cells. Our further molecular characterisation demonstrates that Pak1 activity is increased in myocytes treated with S1P (25 nM) compared with those myocytes without treatment of S1P. By immunoprecipitation we demonstrate that Pak1 and protein phosphatase 2A (PP2A) are associated in ventricular tissue indicating their functional interaction. Thus the results indicate that S1P attenuates beta-adrenergic stress-induced alteration of intracellular Ca2+ release and L-type Ca2+ channel current at least in part via Pak1-PP2A-mediated signalling.

Název v anglickém jazyce

Effect of sphingosine-1-phosphate on L-type calcium current and Ca2+ transient in rat ventricular myocytes

Popis výsledku anglicky

Modulation of Ca2+ homoeostasis in cardiac myocytes plays a major role in beat-to-beat regulation of heart function. Previous studies suggest that sphingosine-1-phosphate (S1P), a biologically active sphingomyelin metabolite, regulates Ca2+ handling in cardiac myocytes, but the underlying mechanism is unclear. In the present study, we tested the hypothesis that S1P-induced functional alteration of intracellular Ca2+ handling includes the L-type calcium channel current (I-Ca,I-L) via a signalling pathway involving P21-activated kinase 1 (Pak1). Our results show that, in rat ventricular myocytes, S1P (100 nM) does not affect the basal activity of I-Ca,I-L but is able to partially reverse the effect of the beta-adrenergic agonist Isoproterenol (ISO, 100 nM) on I-Ca,I-L. S1P (25 nM) also significantly prevents ISO (5 nM)-induced Ca2+ waves and diastolic Ca2+ release in these cells. Our further molecular characterisation demonstrates that Pak1 activity is increased in myocytes treated with S1P (25 nM) compared with those myocytes without treatment of S1P. By immunoprecipitation we demonstrate that Pak1 and protein phosphatase 2A (PP2A) are associated in ventricular tissue indicating their functional interaction. Thus the results indicate that S1P attenuates beta-adrenergic stress-induced alteration of intracellular Ca2+ release and L-type Ca2+ channel current at least in part via Pak1-PP2A-mediated signalling.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular and cellular biochemistry

ISSN

0300-8177

e-ISSN

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Svazek periodika

419

Číslo periodika v rámci svazku

1-2

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

83-92

Kód UT WoS článku

000381208500009

EID výsledku v databázi Scopus

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