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Dysregulation of capacitative calcium entry in hypertensive rats associated to mitochondrial dysfunction
Author(s) -
MéndezLópez I.,
Bomfim G.H.,
Musial DC.,
ArranzTagarro J.A.,
VelascoMartin J.P.,
Jurkiewicz N.H.,
Jurkiewicz A,
García A G,
Padín J.F.
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.845.4
Subject(s) - mitochondrion , ryanodine receptor , endocrinology , medicine , calcium , contractility , thapsigargin , contraction (grammar) , cytosol , intracellular , voltage dependent calcium channel , microbiology and biotechnology , chemistry , biology , biochemistry , enzyme
Mitochondria located in close proximity to high Ca 2+ microdomains are able to buffer it. We hypothesized that this process is impaired in vascular cells inducing adaptive changes, which affect capacitative calcium entry (CCE) and develop a cytosolic calcium overload in spontaneously hypertensive rats (SHR). This conclusion is supported by the following findings in SHR, compared with normotensive Wistar Kyoto rats: 1) augmented contraction of vascular tone by depletion of intracellular Ca 2+ stores with caffeine, ryanodine or thapsigargin in 0 Ca 2+ solutions; 2) the reintroduction of 2.5 Ca 2+ induced higher contractions; 3) these contractions were antagonized by Gd 3+ , La 3+ and SKF‐96365 (a STIM‐1 inhibitor); 4) similar results were obtained in smooth muscular cells (SMC) cultures by fluorescence; 5) western‐blot and immunofluorescence shows STIM‐1 expression up‐regulation both in aorta tissue and SMC; 6) aortic contractility is impaired before FCCP incubation. These results support the hypothesis that mitochondrial dysfunction affect the CCE, an important factor in the calcium overload and cell damage. The cytosolic Ca 2+ overload in SHR due to the mitochondrial failure perform a negative feedback in the store operated channel preventing the Ca 2+ entry. The suppression of this Ca 2+ influx is balanced with a STIM‐1 overexpression, leading to a greater CCE when reticulum depletion occurs. Thus, mitochondria and STIM‐1 could be targets for the treatment of hypertension. Project supported by the following grants to AGG: SAF 2010‐21795, MINECO, Spain; Fundación Teófilo Hernando, Madrid.