Stretch-activated Cation Channels and the Myogenic Response of Small Arteries

Excerpt

Channels sensitive to mechanical stimuli have been suggested to serve as the sensor element of the myogenic response of vascular smooth muscle and to be responsible for the depolarization accompanying the myogenic response. Several candidate channels have been studied. Large conductance calcium-activated potassium channels and voltage-gated calcium channels probably do not contribute to the membrane depolarization associated with the myogenic response. Further, mechano-sensitive chloride channels have been observed in vascular smooth muscle cells and a pressure-induced chloride efflux was reported. However, convincing functional evidence is lacking, because of unspecific effects of the chloride channel inhibitors. Mechano-sensitive nonselective cation channels are the most likely mediators of myogenic depolarization. These channels may belong to the degenerin/epithelial sodium cation channel family and the TRP family, particularly TRPV2, TRPC6, and TRPM4. For the latter two compelling functional evidence for their involvement in the mechanism of myogenic tone has been provided using antisense technology.