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

Published on Dec 12, 2003in Circulation Research15.86
· DOI :10.1161/01.RES.0000106134.69300.B7
Laurent Ferron11
Estimated H-index: 11
,
Véronique Capuano2
Estimated H-index: 2
+ 3 AuthorsJean-François Renaud11
Estimated H-index: 11
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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 (79)
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References41
Newest
#1Véronique Capuano (CNRS: Centre national de la recherche scientifique)H-Index: 2
#2Yann Ruchon (CNRS: Centre national de la recherche scientifique)H-Index: 1
Last.Jean-François Renaud (CNRS: Centre national de la recherche scientifique)H-Index: 17
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#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: 27
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#1Laurent Ferron (CNRS: Centre national de la recherche scientifique)H-Index: 1
#2Véronique Capuano (CNRS: Centre national de la recherche scientifique)H-Index: 2
Last.Jean-François Renaud (CNRS: Centre national de la recherche scientifique)H-Index: 17
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#1Sébastien Lenglet (CNRS: Centre national de la recherche scientifique)H-Index: 23
#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
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#1Gilles Bru-Mercier (CNRS: Centre national de la recherche scientifique)H-Index: 1
#2E. Deroubaix (CNRS: Centre national de la recherche scientifique)H-Index: 8
Last.Jean-François Renaud (CNRS: Centre national de la recherche scientifique)H-Index: 17
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#1Ernesto A. Aiello (UNLP: National University of La Plata)H-Index: 20
#2María C. Villa-Abrille (UNLP: National University of La Plata)H-Index: 13
Last.Horacio E. Cingolani (UNLP: National University of La Plata)H-Index: 33
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Cited By79
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#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.Elie Fadel (French Institute of Health and Medical Research)H-Index: 50
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