Mechanisms underlying the activation of L-type calcium channels by urocortin in rat ventricular myocytes. 2010

Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
Laboratorio de Investigación Cardiovascular, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla 41013, Spain.

OBJECTIVE 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. RESULTS 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D008297 Male Males
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D006727 Hormone Antagonists Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites. Antagonists, Hormone
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
November 2004, Pharmacological research,
Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
August 2003, Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology,
Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
January 2001, Biophysical journal,
Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
April 1997, The American journal of physiology,
Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
January 2024, Biochemical and biophysical research communications,
Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
January 1996, Research communications in molecular pathology and pharmacology,
Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
October 1991, Circulation research,
Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
November 2013, The journal of physiological sciences : JPS,
Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
June 2010, Peptides,
Tarik Smani, and Eva Calderón-Sanchez, and Nieves Gómez-Hurtado, and María Fernández-Velasco, and Victoria Cachofeiro, and Vicente Lahera, and Antonio Ordoñez, and Carmen Delgado
April 2007, Biochemistry and cell biology = Biochimie et biologie cellulaire,
Copied contents to your clipboard!