Match!

Angiotensin II Signaling Pathways Mediate Expression of Cardiac T-Type Calcium Channels

Published on Dec 12, 2003in Circulation Research15.862
· DOI :10.1161/01.RES.0000106134.69300.B7
Laurent Ferron12
Estimated H-index: 12
,
Véronique Capuano4
Estimated H-index: 4
+ 3 AuthorsJean-François Renaud12
Estimated H-index: 12
Abstract
Recent studies indicate that cardiac T-type Ca 2+ current ( I CaT ) reappears in hypertrophied ventricular cells. The aim of this study was to investigate the role of angiotensin II (Ang II), a major inducer of cardiac hypertrophy, in the reexpression of T-type channel in left ventricular hypertrophied myocytes. We induced cardiac hypertrophy in rats by abdominal aorta stenosis for 12 weeks and thereafter animals were treated for 2 weeks with losartan (12 mg/kg per day), an antagonist of type 1 Ang II receptors (AT 1 ). In hypertrophied myocytes, we showed that the reexpressed I CaT is generated by the Ca V 3.1 and Ca V 3.2 subunits. After losartan treatment, I CaT density decreased from 0.40±0.05 pA/pF (n=26) to 0.20±0.03 pA/pF (n=27, P V 3.1- and Ca V 3.2-related currents. The amount of Ca V 3.1 mRNA increased during hypertrophy and retrieved its nonhypertrophic level after losartan treatment, whereas the amount of Ca V 3.2 mRNA was unaffected by stenosis. In cultured newborn ventricular cells, chronic Ang II application (0.1 μmol/L) also increased I CaT density and Ca V 3.1 mRNA amount. UO126, a mitogen-activated protein kinase kinase-1/2 (MEK1/2) inhibitor, reduced Ang II–increased I CaT density and Ca V 3.1 mRNA amount. Bosentan, an endothelin (ET) receptor antagonist, reduced Ang II–increased I CaT density without affecting the amount of Ca V 3.1 mRNA. Finally, cotreatment with bosentan and UO126 abolished the Ang II–increased I CaT density. Our results show that AT 1 -activated MEK pathway and autocrine ET-activated independent MEK pathway upregulate T-type channel expression. Ang II–increased of I CaT density observed in hypertrophied myocytes may play a role in the pathogenesis of Ca 2+ overload and arrhythmias seen in cardiac pathology.
  • References (41)
  • Citations (82)
📖 Papers frequently viewed together
151 Citations
1,252 Citations
284 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References41
Newest
#1Josep M. Colomer (Durham University)H-Index: 5
#2Lan Mao (Duke University)H-Index: 37
Last. Anthony R. Means (Duke University)H-Index: 92
view all 4 authors...
Signals transduced by the multifunctional calcium/calmodulin-dependent protein kinases (CaMKs), have been suggested to regulate the development of hypertrophy. We address the role of the three multifunctional CaMKs, CaMK I, II, and IV, in this process using transverse aortic constriction (TAC) to induce cardiac hypertrophy in mice. We find a 33% increase in total CaMK activity 7 d after TAC. However, there are no changes in the levels of CaMKI, which is expressed in the ventricles, or CaMKIV, wh...
84 CitationsSource
#1Edward Perez-Reyes (UVA: University of Virginia)H-Index: 58
1,252 CitationsSource
#1Orlando F. Bueno (UC: University of Cincinnati)H-Index: 25
#2Jeffery D. Molkentin (UC: University of Cincinnati)H-Index: 109
In response to pathophysiological stress, the adult heart undergoes hypertrophic enlargement characterized by an increase in the cross-sectional area of individual myofibers. Although cardiac hypertrophy is initially a compensatory response, sustained hypertrophy is a leading predictor for the development of heart failure. At the molecular level, disease-related stimuli invoke endocrine, paracrine, and autocrine regulatory circuits, which directly influence cardiomyocyte hypertrophy, in part, th...
321 CitationsSource
#1Véronique Capuano (CNRS: Centre national de la recherche scientifique)H-Index: 3
#2Yann Ruchon (CNRS: Centre national de la recherche scientifique)H-Index: 3
Last. J. F. Renaud (CNRS: Centre national de la recherche scientifique)H-Index: 17
view all 5 authors...
Rats treated with DOCA salts and subjected to abdominal aortic stenosis display left ventricle hypertrophy associated with a decrease in cardiac Ito current density and prolongation of the action potential duration. We investigated the molecular basis of these electrophysiological defects by analyzing the amount of mRNA corresponding to the genes encoding the α subunits of the left ventricle K+ channel at the steady state. The mRNAs corresponding to the α subunits of the K+ channel (Kv1.2, Kv1.4...
27 CitationsSource
#1Gabriel E. Bertolesi (Dal: Dalhousie University)H-Index: 6
#2Chanjuan Shi (Dal: Dalhousie University)H-Index: 31
Last. Melanie E. M. Kelly (Dal: Dalhousie University)H-Index: 28
view all 7 authors...
We show that mitogenic cells expressing T-type Ca2+channels (T-channels) are more sensitive to the antiproliferative effects of the drugs pimozide and mibefradil than cells without significant T-channel expression. The growth of Y79 and WERI-Rb1 retinoblastoma cells, as well as MCF7 breast cancer epithelial cells, all of which express T-channel current and mRNA for T-channel subunits, is inhibited by pimozide and mibefradil with IC50 values between 0.6 and 1.5 μM. Proliferation of glioma C6 cell...
89 CitationsSource
#1Laurent Ferron (CNRS: Centre national de la recherche scientifique)H-Index: 1
#2Véronique Capuano (CNRS: Centre national de la recherche scientifique)H-Index: 3
Last. J. F. Renaud (CNRS: Centre national de la recherche scientifique)H-Index: 17
view all 5 authors...
Abstract T-type calcium current (I CaT ) is distributed among a large variety of species and tissues. The main functions of I CaT are thought to be related to pacemaker activity and to the cell cycle. Using the whole-cell patch-clamp configuration, we showed that fetal rat ventricular cells exhibit an I CaT with electrophysiological and pharmacological characteristics similar to those already described for this current. We investigated I CaT density and found that this current was mainly express...
74 CitationsSource
#1Sebastien Lenglet (CNRS: Centre national de la recherche scientifique)H-Index: 4
#2Estelle Louiset (CNRS: Centre national de la recherche scientifique)H-Index: 2
Last. Vincent Contesse (CNRS: Centre national de la recherche scientifique)H-Index: 6
view all 5 authors...
Serotonin (5-HT) stimulates aldosterone secretion from the rat adrenal gland through 5-HT7 receptors. The aim of the present study was to investigate the transduction mechanisms associated with activation of 5-HT7 receptors in rat glomerulosa cells. The stimulatory effect of 5-HT on aldosterone secretion and cAMP formation was significantly reduced by the 5-HT7 receptor antagonist LY 215840. Pretreatment of cells with the adenylyl cyclase inhibitor SQ 22536 or the PKA inhibitor H-89 markedly att...
52 CitationsSource
#1Gilles Bru-Mercier (CNRS: Centre national de la recherche scientifique)H-Index: 2
#2Edith Deroubaix (CNRS: Centre national de la recherche scientifique)H-Index: 8
Last. J. F. Renaud (CNRS: Centre national de la recherche scientifique)H-Index: 17
view all 5 authors...
The effect of catecholamine depletion (induced by prior treatment with reserpine) was studied in Wistar rat ventricular myocytes using whole cell voltage-clamp methods. Two calcium-independent outward currents, the transient outward potassium current (I to) and the sustained outward potassium current (I sus), were measured. Reserpine treatment decreased tissue norepinephrine content by 97%. Action potential duration in the isolated perfused heart was significantly increased in reserpine-treated ...
17 CitationsSource
#1Ernesto A. Aiello (UNLP: National University of La Plata)H-Index: 22
#2María C. Villa-Abrille (UNLP: National University of La Plata)H-Index: 14
Last. Horacio E. Cingolani (UNLP: National University of La Plata)H-Index: 33
view all 3 authors...
The goal of the present study was to evaluate the effects of Ang II on the current produced by the Na + -Ca 2+ exchanger ( I NCX ) working in the reverse mode and the possible autocrine role played by the release of endothelin (ET) in these actions. I NCX was studied in isolation in cat cardiac myocytes. Angiotensin II (Ang II) (100 nmol/L) increased I NCX at potentials higher than 0 mV (at +60 mV: 2.07±0.22 pA/pF in control versus 2.73±0.22 pA/pF in Ang II, n=9; P I NCX induced by Ang II was pr...
28 CitationsSource
#1Liming Zhang (MHI: Montreal Heart Institute)H-Index: 13
#2Zhiguo Wang (MHI: Montreal Heart Institute)H-Index: 52
Last. Stanley Nattel (McGill University)H-Index: 113
view all 3 authors...
Short-term stimulation of β-receptors is known to affect cardiac ion channels; however, the impact of longer-term stimulation on intrinsic channel function is poorly understood. To evaluate this, cultured guinea pig ventricular myocytes were exposed to isoproterenol (10 nM), vehicle, or isoproterenol plus propranolol (1 μM) for 48 h. Sustained exposure to isoproterenol decreased the density of the inward rectifier (I K1), slow delayed rectifier (I Ks), and L-type Ca2+(I Ca L) currents, effects t...
42 CitationsSource
Cited By82
Newest
1 CitationsSource
view all 4 authors...
Several different procedures may be involved in the arrhythmogenesis in hypertensive patients. There is a complex of hemodynamic changes, neuroendocrine factors, atrial and ventricular structural remodeling, and electrophysiological changes that is thought to contribute to the onset of cardiac arrhythmias. In this review, we are going to summarize the current state of knowledge based on the latest literature.
Source
Pulmonary arterial hypertension (PAH) is a multifactorial and severe disease without curative therapies. PAH pathobiology involves altered pulmonary arterial tone, endothelial dysfunction, distal pulmonary vessel remodeling, and inflammation, which could all depend on ion channel activities (K+, Ca2+, Na+ and Cl−). This review focuses on ion channels in the pulmonary vasculature and discusses their pathophysiological contribution to PAH as well as their therapeutic potential in PAH.
8 CitationsSource
#1Paolo VerdecchiaH-Index: 67
#2Fabio AngeliH-Index: 35
Last. Gianpaolo ReboldiH-Index: 46
view all 3 authors...
Hypertension and atrial fibrillation (AF) are 2 important public health priorities. Their prevalence is increasing worldwide, and the 2 conditions often coexist in the same patient. Hypertension an...
11 CitationsSource
#1Alexander KushnirH-Index: 7
#2Steven O. MarxH-Index: 39
Source
#1D. Falcón (University of Seville)H-Index: 2
#2R. González-Montelongo (University of Seville)H-Index: 1
Last. Antonio Castellano (University of Seville)H-Index: 19
view all 6 authors...
Abstract Glucocorticoids are widely used to treat acute and chronic diseases. Unfortunately, their therapeutic use is associated with severe side effects. Glucocorticoids are known to regulate several ion channels in cardiac myocytes, including voltage-dependent Ca2+ channels. Low-voltage-activated T-type Ca2+ channels are expressed in ventricular myocytes during the fetal and perinatal period, but are practically absent in the adult. However, these channels can be re-expressed in adult cardiomy...
2 CitationsSource
In patients with thalassemia, iron overload cardiomyopathy is a major cause of cardiac dysfunction and mortality. Despite many advances in the development of new iron chelating agents, heart failure still occurs in some patients and can lead to an increase in mortality rate. Recently, potential novel therapeutic strategies in the treatment of these patients have focused on L-type and T-type calcium channel blockers. These 2 channels have been reported as being the main routes for cardiac iron up...
2 CitationsSource
#1Safietou Sankhe (French Institute of Health and Medical Research)H-Index: 1
#2Sevasti Manousakidi (French Institute of Health and Medical Research)H-Index: 1
Last. Véronique Capuano (French Institute of Health and Medical Research)H-Index: 4
view all 15 authors...
Abstract Idiopathic pulmonary arterial hypertension (iPAH) is characterized by obstructive hyperproliferation and apoptosis resistance of distal pulmonary artery smooth muscle cells (PASMCs). T-type Ca 2 + channel blockers have been shown to reduce experimental pulmonary hypertension, although the impact of T-type channel inhibition remains unexplored in PASMCs from iPAH patients. Here we show that T-type channels Cav3.1 and Cav3.2 are present in the lung and PASMCs from iPAH patients and contro...
4 CitationsSource
1 CitationsSource
#1Juan Tamargo (Complutense University of Madrid)H-Index: 62
#2Luis M. RuilopeH-Index: 79
ABSTRACTIntroduction: Voltage-gated Ca2+ channels are the primary route of Ca2+ entry in vascular smooth muscle cells, playing a key role in the regulation of arterial tone and blood pressure. Since the 60´s, L-type Ca2+ channel blockers (CCBs) have been widely used for the treatment of hypertension.Areas covered: T-type Ca2+ channels regulate vascular tone in small-resistance vessels and aldosterone secretion, and N-type channels expressed in sympathetic nerve terminals regulate the release of ...
1 CitationsSource