1 Kardiovaskulær og Renal Forskning, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU2 Nephrology, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU3 unknown4 Kardiovaskulær og Renal Forskning, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU
Recent preclinical data indicate that activators of transient receptor potential channels of the vanilloid receptor subtype 1 (TRPV1) may improve the outcome of ischaemic acute kidney injury (AKI). The underlying mechanisms are unclear, but may involve TRPV1 channels in dorsal root ganglion neurones that innervate the kidney. Recent data identified TRPV4, together with TRPV1, to serve as major calcium influx channels in endothelial cells. In these cells, gating of individual TRPV4 channels within a four-channel cluster provides elementary calcium influx (calcium sparklets) to open calcium-activated potassium channels and promote vasodilation. The TRPV receptors can also form heteromers that exhibit unique conductance and gating properties, further increasing their spatio-functional diversity. This review summarizes data on electrophysiological properties of TRPV1/4 and their modulation by endogenous channel agonists such as 20-HETE, phospholipase C and phosphatidylinositide 3-kinase (PI3 kinase). We review important roles of TRPV1 and TRPV4 in kidney physiology and renal ischaemia reperfusion injury; further studies are warranted to address renoprotective mechanism of vanilloid receptors in ischaemic AKI including the role of the capsaicin receptor TRPV1 in primary sensory nerves and/or endothelium. Particular attention should be paid to understand the kidneys' ability to respond to ischaemic stimuli after catheter-based renal denervation therapy in man, whereas the discovery of novel pharmacological TRPV modulators may be a successful strategy for better treatment of acute or chronic kidney failure.
Acta Physiologica (print), 2013, Vol 207, Issue 3, p. 546-564