Eva Calderón-Sanchez

Publications (2)11.6 Total impact

• Article: Mechanisms underlying the activation of L-type calcium channels by urocortin in rat ventricular myocytes.

  Tarik Smani, Eva Calderón-Sanchez, Nieves Gómez-Hurtado, María Fernández-Velasco, Victoria Cachofeiro, Vicente Lahera, Antonio Ordoñez, Carmen Delgado
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  ABSTRACT: The aim of this study was to elucidate the signalling pathways implicated in the modulation of cardiac L-type Ca(2+) channels by urocortin (Ucn) in ventricular myocytes. Adult rat ventricular myocytes were stimulated in vitro with Ucn for 20-40 min. L-type calcium currents (I(CaL)) were measured with the patch-clamp technique, whereas quantification of activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was assessed by sandwich-ELISA. Ucn induced a significant increase in I(CaL) density that was not prevented by the protein kinase A (PKA) inhibitor KT-5720 or the non-selective antagonist of guanine nucleotide exchange factor brefeldin A. The Ucn effect was antagonized by astressin, a corticotropin-releasing factor receptor-2 (CRF-R2) antagonist, and significantly reduced by protein kinase C (PKC) and ERK1/2 inhibitors. The cyclic AMP (cAMP) analogue 8-pCPT-2'OMe-cAMP, which selectively activates the exchange protein activated by cAMP (Epac), was ineffective in modifying I(CaL). Analysis of phospho-ERK1/2 showed that Ucn induced a significant activation of the ERK1/2 pathway in ventricular myocytes and this effect was prevented by pre-incubation with PKC inhibitors. The present study provides evidence of new mechanisms involved in the modulation of L-type Ca(2+) channels by Ucn in adult ventricular myocytes. We propose that the marked increase in I(CaL) density induced by Ucn is mediated through CRF-R2 and involves PKC-dependent activation of the ERK1/2 pathway, whereas PKA and Epac signalling are not implicated.
  Cardiovascular research 02/2010; 87(3):459-66. · 5.80 Impact Factor
• Article: Urocortin induces positive inotropic effect in rat heart.

  Eva Calderón-Sanchez, Carmen Delgado, Gema Ruiz-Hurtado, Alejandro Domínguez-Rodríguez, Victoria Cachofeiro, María Rodríguez-Moyano, Ana María Gomez, Antonio Ordóñez, Tarik Smani
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  ABSTRACT: The aim of this study is to evaluate the positive inotropic effect of urocortin (Ucn) and to characterize its signalling pathways. Contractility was measured in ex vivo Langendorff-perfused hearts isolated from Wistar rats. Isolated ventricular cardiomyocytes were used to analyse intracellular calcium ([Ca(2+)](i)) transients evoked by electrical stimulation and L-type Ca(2+) current by confocal microscopy and whole-cell patch-clamping, respectively. The application of Ucn to perfused hearts induced progressive, sustained, and potent inotropic and lusitropic effects that were dose-dependent with an EC(50) of approximately 8 nM. Ucn effects were independent of protein kinase A (PKA) activation but were significantly reduced by protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) inhibitors and by brefeldin A, an antagonist of guanine nucleotide exchange factor, suggested to be an inhibitor of exchange protein activated by cAMP (Epac). These whole-organ effects were correlated with the inotropic effects observed in isolated cells: Ucn increased I(CaL) density, [Ca(2+)](i) transients, cell shortening and Ca(2+) content of sarcoplasmic reticulum. Our results show that Ucn evokes potent positive inotropic and lusitropic effects mediated, at least in part, by an increase in I(CaL) and [Ca(2+)](i) transient amplitude. These effects may involve the activation of Epac, PKC, and MAPK signalling pathways.
  Cardiovascular research 06/2009; 83(4):717-25. · 5.80 Impact Factor