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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

OBJECTIVES - Adenosine is a cAMP-elevating vasodilator that induces both endothelium-dependent and -independent vasorelaxation. An increase in cytosolic Ca ([Ca]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 Ca influx in vascular endothelial cells. METHODS AND RESULTS - Adenosine-induced Ca 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 Ca 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 Ca influx and the cation current in H5V cells. Furthermore, L-cis-diltiazem inhibited the endothelial Ca 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 Ca influx and vasorelaxation. It is likely that adenosine acts through A2B receptors and adenylyl cyclases to stimulate CNGA2.

Original languageEnglish (US)
Pages (from-to)913-918
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume28
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Keywords

  • Adenosine
  • CNGA2 channels
  • Ca
  • Endothelial cells
  • cAMP

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