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Localization and function of connexin 45 in the renal cortical vasculature
Author(s) -
Hanner Fiona Pamela,
Toma Ildiko,
Sipos Arnold,
Vargas Sarah,
PetiPeterdi Janos
Publication year - 2008
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.22.1_supplement.761.9
Subject(s) - afferent arterioles , gap junction , chemistry , macula densa , connexin , suramin , medicine , renal cortex , endocrinology , angiotensin ii , renin–angiotensin system , kidney , intracellular , microbiology and biotechnology , receptor , biology , blood pressure , biochemistry
Connexins (Cx) play an important role in cell to cell communication via intercellular gap junction channels or transiently open pores (hemichannels). We studied Cx45 in the mouse kidney using conditional Cx45‐deficient (Cx45fl/fl:Nestin‐Cre) mice expressing EGFP in place of Cx45 in cells that during development expressed the intermediate filament nestin. EGFP fluorescence was found in the afferent and efferent arteriolar vascular smooth muscle (VSMC) and renin producing JG cells and in the extra and intraglomerular mesangium indicating that Cx45 is normally expressed in the juxtaglomerular apparatus (JGA). Immunoblotting detected a 1.5‐fold increase in renal cortical renin content in Cx45−/− mice. Wild type and Cx45−/− VSMCs were cultured from dissected afferent arteriole explants. Cells were loaded with Fluo‐4/Fura red and ratiometric [Ca 2+ ] i imaging was performed using fluorescence confocal microscopy. Mechanical stimulation of a single VSMC caused a 5‐fold increase in [Ca 2+ ] i which propagated from cell to cell throughout the monolayer (12.6±1.1 μm/s) over distances >400 μm. In VSMCs from Cx45−/− mice Ca 2+ wave propagation was significantly inhibited with velocity of 7±1 μm/s and peak [Ca 2+ ] i =56.21±15 (n=6). Addition of either the purinergic receptor antagonist suramin or the Cx blocker 18‐alpha GA reduced Ca 2+ wave propagations. Cx45 plays an important role in renal vascular control, renin release and JGA function.