Epinephrine-induced Ca2+ influx in vascular endothelial cells is mediated by CNGA2 channels

Bing Shen, Kwong Tai Cheng, Yuk Ki Leung, Yuk Chi Kwok, Hiu Yee Kwan, Ching On Wong, Zhen Yu Chen, Yu Huang, Xiaoqiang Yao*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

30 Citations (Scopus)


Epinephrine, through its action on β-adrenoceptors, may induce endothelium-dependent vascular dilation, and this action is partly mediated by a cytosolic Ca2+ ([Ca2+]i) change in endothelial cells. In the present study, we explored the molecular identity of the channels that mediate epinephrine-induced endothelial Ca2+ influx and subsequent vascular relaxation. Patch clamp recorded an epinephrine- and cAMP-activated cation current in the primary cultured bovine aortic endothelial cells (BAECs) and H5V endothelial cells. L-cis-diltiazem and LY-83583, two selective inhibitors for cyclic nucleotide-gated channels, diminished this cation current. Furthermore, this cation current was greatly reduced by a CNGA2-specific siRNA in H5V cells. With the use of fluorescent Ca2+ dye, it was found that epinephrine and isoprenaline, a β-adrenoceptor agonist, induced endothelial Ca2+ influx in the presence of bradykinin. This Ca2+ influx was inhibited by L-cis-diltiazem and LY-83583, and by a β2-adrenoceptor antagonist ICI-118551. CNGA2-specific siRNA also diminished this Ca2+ influx in H5V cells. Furthermore, L-cis-diltiazem and LY-83583 inhibited the endothelial Ca2+ influx in isolated mouse aortic strips. L-cis-diltiazem also markedly reduced the endothelium-dependent vascular dilation to isoprenaline in isolated mouse aortic segments. In summary, CNG channels, CNGA2 in particular, mediate β-adrenoceptor agonist-induced endothelial Ca2+ influx and subsequent vascular dilation.

Original languageEnglish
Pages (from-to)437-445
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Issue number3
Publication statusPublished - Sept 2008

Scopus Subject Areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

User-Defined Keywords

  • Ca2+
  • CNGA2 channels
  • Endothelial cells
  • Epinephrine
  • Isoprenaline


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