Premium
Angiotensin II activates two distinct cation conductances in a concentration dependent manner which display TRPC like properties
Author(s) -
Saleh Sohag Nafis,
Albert Anthony P,
Wildman Claire M Peppiatt,
Large William A
Publication year - 2007
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.21.5.a537-c
Subject(s) - trpc , trpc6 , trpc1 , losartan , angiotensin ii , chelerythrine , chemistry , angiotensin ii receptor type 1 , myocyte , transient receptor potential channel , endocrinology , medicine , activator (genetics) , biophysics , receptor , protein kinase c , biochemistry , biology , signal transduction
This study was aimed at investigating the effects of the potent vasoconstrictor angiotensin II (Ang II) in freshly dispersed smooth muscle myocytes of the rabbit mesenteric artery. In the cell‐attached configuration 1nM Ang II activated cation channel currents ( I cat1 ) with three conductance states of about 15, 30 and 45 pS. However, 100nM Ang II inhibited I cat1 but evoked another cation channel with a conductance of 2 pS ( I cat2 ). The AT1 receptor antagonist losartan and the PLC inhibitor U73122 blocked Ang II‐evoked I cat1 and I cat2 . The PKC inhibitor chelerythrine potentiated Ang II‐evoked I cat1 and inhibited I cat2 whereas the PKC activator PDBu reduced Ang II‐induced I cat1 but activated I cat2 . Agents that deplete intracellular Ca 2+ stores also activated a cation current with similar properties to I cat2 . Bath application of anti‐TRPC6 and anti‐TRPC1 antibodies to inside‐out patches inhibited I cat1 and I cat2 respectively. Immunocytochemical studies showed TRPC6 and TRPC1 expression with TRPC6 preferentially distributed in the plasma membrane and TRPC1 expression located throughout the cell. These results indicate that Ang II activates two distinct cation conductances in mesenteric artery myocytes and it is proposed that TRPC6 and TRPC1 channel proteins are important components of Ang II‐induced I cat1 and I cat2 respectively. Funded by the British Heart Foundation and the Wellcome Trust.