Epinephrine-induced Ca2+ influx in vascular endothelial cells is mediated by CNGA2 channels.
Epinephrine, through its action on beta-adrenoceptors, may induce endothelium-dependent vascular dilation, and this action is partly mediated by a cytosolic Ca(2+) ([Ca(2+)](i)) change in endothelial cells. In the present study, we explored the molecular identity of the channels that mediate epinephrine-induced endothelial Ca(2+) 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 Ca(2+) dye, it was found that epinephrine and isoprenaline, a beta-adrenoceptor agonist, induced endothelial Ca(2+) influx in the presence of bradykinin. This Ca(2+) influx was inhibited by L-cis-diltiazem and LY-83583, and by a beta(2)-adrenoceptor antagonist ICI-118551. CNGA2-specific siRNA also diminished this Ca(2+) influx in H5V cells. Furthermore, L-cis-diltiazem and LY-83583 inhibited the endothelial Ca(2+) 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 beta-adrenoceptor agonist-induced endothelial Ca(2+) influx and subsequent vascular dilation.
Shen
Bing
B
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Cheng
Kwong-Tai
KT
Leung
Yuk-Ki
YK
Kwok
Yuk-Chi
YC
Kwan
Hiu-Yee
HY
Wong
Ching-On
CO
Chen
Zhen-Yu
ZY
Huang
Yu
Y
Yao
Xiaoqiang
X
D000818:Animals; D001013:Aorta, Thoracic; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism*; D004837:Epinephrine / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D014664:Vasodilation / Q000502:physiology
C518240:Cnga2 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D002118:Calcium; D004837:Epinephrine