Lipid-Mediated Mechanisms Involved in the Mechanical Activation of TRPC6 and TRPV4 Channels in the Vascular Tone Regulation

The transient receptor potential (TRP) proteins form a large Ca2+-permeable nonselective cation channel superfamily activated by physicochemical stimuli, and participate in a wide array of biological functions including sensory signal transduction. Recent investigations have disclosed that many of TRP channels expressed in the cardiovascular system (CVS) are activated by mechanical stresses operating therein such as membrane stretch, hypoosmolarity and shear stress. Although mechanisms proposed for mechanical signal transduction are diverse, accumulating evidence suggests that lipid mediators derived from phospholipase C (PLC)- and phospholipase A2 (PLA2)-dependent pathways may play central roles in the activation and regulation of these TRP channels. In this review, we focus on the lipid-mediated regulation of two TRP channels abundantly expressed in the CVS, i.e. TRPC6 and TRPV4, with particular interest in the synergistic interaction between receptor-mediated and mechanical stimulations, and discuss about their complex functional antagonism in vascular tone and blood pressure regulation.