A mechanosensitive cation channel in endothelial cells and its role in vasoregulation

Ca²⁺ is an important intracellular second messenger in signal transduction of endothelial cells. It has long been recognized that a mechanosensitive Ca²⁺-permeable channel is present in vascular endothelial cells. The activity of this channel may increase intracellular Ca²⁺ level in endothelial cells. A recent finding is that the activity of this channel may be regulated by cGMP through a protein kinase G-dependent pathway. Inhibition of the channel by cGMP abolishes the Ca²⁺ influx elicited by flow. Several inhibitors of the cation channel including Gd³⁺, Ni²⁺, and SK&F-96365 also inhibit the Ca²⁺ influx due to flow stimulation. These data suggest that a mechanosensitive cation channel is the primary pathway mediating the flow-induced Ca²⁺ entry in vascular endothelial cells. Another important finding is that the opening of this mechanosensitive channel by KT5823 leads to endothelium-dependent vascular dilation. Therefore, it appears that this channel may play a crucial role in the regulation of vascular tone.