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TRPC1‐deficiency amplifies EDHF‐type dilations in mice
Author(s) -
Schmidt Kjestine,
Dubrovska Galyna,
Nielsen Gorm,
Fesüs Gabor,
Uhrenholt Torben R,
Hansen Pernille B,
Gudermann Thomas,
Dietrich Alexander,
Gollasch Maik,
Wit Cor,
Kohler Ralf
Publication year - 2011
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.25.1_supplement.814.10
The endothelium releases NO, prostacyclin, and an endothelium‐derived hyperpolarizing factor (EDHF). EDHF requires endothelial hyperpolarisation through the opening of Ca 2+ ‐activated K + ‐channels (K Ca ). Thus, Ca 2+ ‐permeable transient receptor potential channels (TRP) may contribute. We studied dilations in the microcirculation and in carotid arteries in wildtype and TRPC1‐deficient mice (TRPC1 −/− ). Ca 2+ sparks and spontaneous transient outward currents (STOCs) were measured in isolated smooth muscle cells (SMC) and systolic blood pressure (SBP) using tail‐cuff plethysmography. In the presence of Nitro‐L‐arginine and indomethacin spontaneous arteriolar diameter was larger in TRPC1 −/− in vivo . ACh‐induced EDHF‐type dilations were augmented in TRPC1 −/− arterioles as indicated by a shift of the EC 50 but dilations to nitroprusside and adenosine were unchanged. Likewise, TRPC1‐deficiency amplified ACh‐induced EDHF‐type dilations in carotid arteries in vitro but not ACh‐induced NO‐mediated dilations. Ca 2+ ‐sparks and BK Ca ‐mediated STOCs in isolated SMC as well as constrictions to phenylephrine in vessels were equivalent in both genotypes. SBP was lower in TRPC1 −/− . Our data show specifically enhanced EDHF‐type dilations in TRPC1 −/− mice despite preserved smooth muscle function. This suggests that TRPC1 acts as a negative regulator in the endothelial K Ca /EDHF‐type signalling complex.