TRPV2 Channels Contribute to Stretch-Activated Cation Currents and Myogenic Constriction in Retinal Arterioles

Abstract

Our results suggest that retinal VSMCs express a range of mechanosensitive TRP channels, but only TRPV2 appears to contribute to myogenic signaling in this vascular bed.

Voltage vs. Ligand I: Structural basis of the intrinsic flexibility of S3 segment and its significance in ion channel activation

“…Some of the S3 profiles with more pronounced rigidity are members of the TRPV, Hv1, and KCNQ families, as well as domains DIII and DIV of Na V 1 channels (Figure 1). In accordance with our prediction on S3 rigidity facilitating mechanosensitivity, KCNQ channels, TRPV2 and Hv1 have recently been recognized as directly activated by the membrane stretching [95][96][97][98]. In Hv1 proton channels, for which the whole VSD is the more rigid in the VGIC superfamily (see Figure 1, top panel), the effect of negative pressure of -10 mmHg in the pipette clearly shifts the activation curve ∼14.5 mV [98].…”

TRPV2 channel inhibitors attenuate fibroblast differentiation and contraction mediated by keratinocyte-derived TGF-β1 in an in vitro wound healing model of rats

“…Such actions of SKF96365 were similar to those of LY364947. Other TRP inhibitors and activators at concentrations that have been reported to be effective, such as the TRPV1-3 activator 2-APB (100 mM) [33,34], TRPV1 activator capsaicin (100 nM) [35], TRPV4 activator GSK1016790A (25 nM) [36,37], TRPV1 inhibitor AMG9810 (10 mM) [32], and TRPV4 inhibitors RN1734 (10 mM) [38] and HC067047 (1 mM) [36,39], exhibited smaller actions. A cell viability assay revealed that these compounds did not significantly alter the viability index of dermal fibroblasts to account for their action on gel contraction (Suppl.…”

“…Tranilast has been used clinically for the prevention of hypertrophic scar formation [27]. This compound was reported to inhibit TRPV2 channels [24,39]. Here, we tested the effects of SKF96365 and tranilast on fibroblast differentiation and contraction of the KC(+) model.…”

“…Originally, TRPV2 was described as a noxious heat thermosensor that is activated by chemical reagents, such as 2-APB and cannabinoids [47], but several reports point toward a function for TRPV2 as a mechanosensor in aortic myocytes and neurons [48,49]. Stretchtriggered cation channels were shown to be blocked by the TRPV2 inhibitor tranilast in retinal arterioles [39]. Furthermore, several growth factors (insulin and insulin-like growth factor-1) and serum induced the translocation of TRPV2 from an intracellular compartment to the plasma membrane, which was inhibited by tranilast [23,24].…”

Functions of sensory TRP channels in vascular responses to chemical and thermal stimuli

“…Other TRP channels such as TRPV2 have been proposed to play an important role in the stretch-activated cation currents and myogenic constriction in retinal arterioles [163].…”