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ROLE OF ENDOTHELIAL CANONICAL TRANSIENT RECEPTOR POTENTIAL (TRPC) CHANNELS IN ATP‐MEDIATED VASORELAXATION
Author(s) -
Marrelli Sean P,
Kochukov Mikhail Y,
Noel Rebecca C,
Mbaka Maryann M,
Chen Jie
Publication year - 2010
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.24.1_supplement.976.11
Subject(s) - trpc , transient receptor potential channel , chemistry , vascular smooth muscle , biophysics , endothelial stem cell , microbiology and biotechnology , endothelium , myograph , calcium , adenosine triphosphate , phenylephrine , biochemistry , medicine , receptor , endocrinology , biology , smooth muscle , organic chemistry , blood pressure , in vitro
Adenosine triphosphate (ATP) is a physiological agonist that is released from multiple sources in the vascular system including red blood cells, endothelial cells, and vascular smooth muscle cells. ATP can elicit an endothelium‐dependent vasorelaxation, however, the mechanism is still unresolved. The present study examines the role of TRPC channels in the mechanism of ATP‐mediated vasorelaxation. Experiments were performed with mouse aorta and aorta endothelial cells. Aorta contractions and relaxations were measured by artery myography. Freshly isolated endothelial cells were used for the measurement of endothelial calcium by fluorescent dye (Fura 2) and non‐selective cation currents by whole cell patch clamp. ATP produced a concentration‐dependent (EC 50 = 2 μM) relaxation in phenylephrine (3 μM) pre‐contracted arteries. In isolated endothelial cells, ATP (10 to 100 μM) stimulated a non‐selective cation current (I ATP ) that was inhibited by La 3+ or Gd 3+ (each 100 μM). ATP also produced an increase in endothelial calcium that was inhibited by La 3+ (100 μM) or 2‐APB (100 μM). In summary, we present evidence that ATP stimulates vasorelaxation subsequent to endothelial cell calcium entry via TRPC‐like channels. Further studies with genetic mouse models will test the roles of specific TRPC channels in the mechanism. Supported by NIH R01 HL088435 to SPM.