TY - JOUR
T1 - A protein kinase G-sensitive channel mediates flow-induced Ca2+ entry into vascular endothelial cells
AU - Yao, Xiaoqiang
AU - Kwan, Hiu Yee
AU - Chan, Franky Leung
AU - Chan, Nickie Wai Kei
AU - Huang, Yu
N1 - This study was supported by grants from National Heart Foundation H1999013 and from Hong Kong Research Grant Council CUHK4259/99M.
PY - 2000/5
Y1 - 2000/5
N2 - The hemodynamic force generated by blood flow is considered to be the physiologically most important stimulus for the release of nitric oxide (NO) and prostacyclin (PGI2) from vascular endothelial cells (1). NO and PGI2 then act on the underlying smooth muscle cells, causing vasodilation and thus lowering blood pressure (2, 3). One critical early event occurring in this flow-induced regulation of vascular tone is that blood flow induces Ca2+ entry into vascular endothelial cells, which in turn leads to the formation of NO (4, 5). Here we report a mechanosensitive Ca2+-permeable channel in vascular endothelial cells. The activity of the channel was inhibited by 8- Br-cGMP, a membrane-permeant activator of protein kinase G (PKG), in cell- attached membrane patches. The inhibition could be reversed by PKG inhibitor KT5823 or H-8. A direct application of active PKG in inside-out patches blocked the channel activity. Gd3+, Ni2+, or SK and F-96365 also inhibited the channel activity. A study of fluorescent Ca2+ entry revealed a striking pharmacological similarity between the Ca2+ entry elicited by flow and the mechanosensitive Ca2+-permeable channel we identified, suggesting that this channel is the primary pathway mediating flow-induced Ca2+ entry into vascular endothelial cells.
AB - The hemodynamic force generated by blood flow is considered to be the physiologically most important stimulus for the release of nitric oxide (NO) and prostacyclin (PGI2) from vascular endothelial cells (1). NO and PGI2 then act on the underlying smooth muscle cells, causing vasodilation and thus lowering blood pressure (2, 3). One critical early event occurring in this flow-induced regulation of vascular tone is that blood flow induces Ca2+ entry into vascular endothelial cells, which in turn leads to the formation of NO (4, 5). Here we report a mechanosensitive Ca2+-permeable channel in vascular endothelial cells. The activity of the channel was inhibited by 8- Br-cGMP, a membrane-permeant activator of protein kinase G (PKG), in cell- attached membrane patches. The inhibition could be reversed by PKG inhibitor KT5823 or H-8. A direct application of active PKG in inside-out patches blocked the channel activity. Gd3+, Ni2+, or SK and F-96365 also inhibited the channel activity. A study of fluorescent Ca2+ entry revealed a striking pharmacological similarity between the Ca2+ entry elicited by flow and the mechanosensitive Ca2+-permeable channel we identified, suggesting that this channel is the primary pathway mediating flow-induced Ca2+ entry into vascular endothelial cells.
KW - Blood flow
KW - Endothelium
KW - Nonselective cation channel
KW - Shear stress
UR - http://europepmc.org/abstract/med/10783147
UR - http://www.scopus.com/inward/record.url?scp=0034097188&partnerID=8YFLogxK
U2 - 10.1096/fasebj.14.7.932
DO - 10.1096/fasebj.14.7.932
M3 - Journal article
C2 - 10783147
AN - SCOPUS:0034097188
SN - 0892-6638
VL - 14
SP - 932
EP - 938
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -