The Contribution of TRPV4-Mediated Calcium Signaling to Calcium Homeostasis in Endothelial Cells

Abstract

A large variety of cation transport systems are involved in the regulation of calcium homeostasis in endothelial cells. The focus of the present study is to determine the contribution of nonselective cation channels from the TRP (transient receptor potential) family to cellular calcium homeostasis of porcine aortic endothelial cells (PAEC). One member of the TRPV (vanniloid) subfamily, TRPV4, has previously been shown to be involved in cation transport induced by a large variety of stimulations including osmolarity, temperature, mechanical stress, and phosphorylation. Here, we demonstrate the existence of several TRP proteins, including TRPV4, in PAEC using RT-PCR. To test whether this channel is functional, we performed FURA-2 calcium measurements and whole-cell patch-clamp experiments. We observed the induction of large calcium signals following mechanical stress, altered extracellular temperature, and the selective TRPV4 activator 4-alpha -PDD. These effects were diminished in the presence of the TRPV4 inhibitor miconazole, suggesting the involvement of this channel in mediating endothelial calcium signals. The large amounts of transported calcium and the short signaling ways suggest a potentially important role of this channel in many physiological processes.

A role for transient receptor potential vanilloid 4 in tonicity‐induced neurogenic inflammation

“…1170 N Vergnolle et al SP-stimulated granulocyte recruitment may account for the increased MPO activity in tissues. However, TRPV4 is also expressed by cell types other than neurones, such as endothelial cells ( Watanabe et al, 2002b;Chung et al, 2003;Fian et al, 2007). Thus, although our results strongly suggest that TRPV4 agonists promote oedema and granulocyte recruitment by a neurogenic mechanism, we cannot exclude the possibility that hypotonic solution and 4aPDD directly activate TRPV4 on endothelial cells to cause inflammation.…”

“…Such compensatory mechanisms could mask a complete inhibition of oedema. Although intrathecal siRNA acutely diminished expression of TRPV4 in DRG neurones, thus reducing the likelihood of compensation, intraplantar hypotonic solutions and 4aPDD may activate TRPV4 in other cell types, such as endothelial cells or keratinocytes, to induce oedema (Watanabe et al, 2002b;Chung et al, 2003;Fian et al, 2007). TRPV4 knockdown or deletion abolished hypotonic solution-and 4aPDD-induced granulocyte recruitment.…”

Thermosensitive transient receptor potential channels in human corneal epithelial cells

“…For example, TRPV4 has been described in endothelial cells and corneal epithelial cells (Fian et al, 2007;Hartmannsgruber et al, 2007;Kohler et al, 2006;Yao and Garland, 2005;Pan et al, 2008). TRPV3-4 expression was also observed in skin epidermal keratinocytes (Chung et al, 2003;Peier et al, 2002) and TRPV3 has been recently described in mouse distal colon epithelium and in the mouse cornea as well as in the HCEC (Ueda et al, 2009;Yamada et al, 2009).…”

Update on vascular endothelial Ca2+signalling: A tale of ion channels, pumps and transporters

“…More specifically, TRPV4-gated Ca 2+ entry increases vascular permeability to such an extent that barrier disruption and alveolar flooding may occur [313] . Finally, TRPV4 may enable ECs to sense body temperature, because the threshold for the heat-dependent activation for this channel is set at 25-27 ℃ and it is activated by moderate heat in ECs [4,288,317,318] . The results provided by knocked out mice, however, suggest that the steady state release of NO from endothelium is not governed by such a mechanism.…”