CNGA2 channels mediate adenosine-induced Ca2+ influx in vascular endothelial cells

Kwong Tai Cheng, Yuk Ki Leung, Bing Shen, Yuk Chi Kwok, Ching On Wong, Hiu Yee Kwan, Yu Bun Man, Xin Ma, Yu Huang, Xiaoqiang Yao*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

23 Citations (Scopus)


Objectives  Adenosine is a cAMP-elevating vasodilator that induces both endothelium-dependent and -independent vasorelaxation. An increase in cytosolic Ca2+ ([Ca2+]i) is a crucial early signal in the endothelium-dependent relaxation elicited by adenosine. This study explored the molecular identity of channels that mediate adenosine-induced Ca2+ influx in vascular endothelial cells.

Methods and Results  Adenosine-induced Ca2+ influx was markedly reduced by L-cis-diltiazem and LY-83583, two selective inhibitors for cyclic nucleotide-gated (CNG) channels, in H5V endothelial cells and primary cultured bovine aortic endothelial cells (BAECs). The Ca2+ influx was also inhibited by 2 adenylyl cyclase inhibitors MDL-12330A and SQ-22536, and by 2 A2B receptor inhibitors MRS-1754 and 8-SPT, but not by an A2A receptor inhibitor SCH-58261 or a guanylyl cyclase inhibitor ODQ. Patch clamp experiments recorded an adenosine-induced current that could be inhibited by L-cis-diltiazem and LY-83583. A CNGA2-specific siRNA markedly decreased the Ca2+ influx and the cation current in H5V cells. Furthermore, L-cis-diltiazem inhibited the endothelial Ca2+ influx in mouse aortic strips, and it also reduced 5-N-ethylcarboxamidoadenosine (NECA, an A2 adenosine receptor agonist)-induced vasorelaxation.

Conclusion  CNGA2 channels play a key role in adenosine-induced endothelial Ca2+ influx and vasorelaxation. It is likely that adenosine acts through A2B receptors and adenylyl cyclases to stimulate CNGA2.

Original languageEnglish
Pages (from-to)913-918
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number5
Publication statusPublished - May 2008

Scopus Subject Areas

  • Cardiology and Cardiovascular Medicine

User-Defined Keywords

  • Adenosine
  • Ca2+
  • cAMP
  • CNGA2 channels
  • Endothelial cells


Dive into the research topics of 'CNGA2 channels mediate adenosine-induced Ca2+ influx in vascular endothelial cells'. Together they form a unique fingerprint.

Cite this