Abstract
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.
Original language | English |
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Pages (from-to) | 932-938 |
Number of pages | 7 |
Journal | FASEB Journal |
Volume | 14 |
Issue number | 7 |
DOIs | |
Publication status | Published - May 2000 |
Scopus Subject Areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
User-Defined Keywords
- Blood flow
- Endothelium
- Nonselective cation channel
- Shear stress