Background and Purpose: Heat-sensitive transient receptor potential vanilloid (TRPV) channels are expressed in various epithelial tissues regulating, among else, barrier functions. Their expression is well established in the distal nephron; however, we have no data about their presence in podocytes. As podocytes are indispensable in the formation of the glomerular filtration barrier, we investigated the presence and function of Ca2+-permeable TRPV1–4 channels in human podocyte cultures. Experimental Approach: Expression of TRPV1–4 channels was investigated at protein (immunocytochemistry, Western blot) and mRNA (Q-PCR) level in a conditionally immortalized human podocyte cell line. Channel function was assessed by measuring intracellular Ca2+ concentration using Flou-4 Ca2+-indicator dye and patch clamp electrophysiology upon applying various activators and inhibitors. Key Results: Thermosensitive TRP channels were expressed in podocytes. The TRPV1-specific agonists capsaicin and resiniferatoxin did not affect the intracellular Ca2+ concentration. Cannabidiol, an activator of TRPV2 and TRPV4 channels, induced moderate Ca2+-influxes, inhibited by both tranilast and HC067047, blockers of TRPV2 and TRPV4 channels respectively. The TRPV4-specific agonists GSK1016790A and 4α-phorbol 12,13-didecanoate induced robust Ca2+-signals which were abolished by HC067047. Non-specific agonists of TRPV3 channels induced marked Ca2+ transients. However, TRPV3 channel blockers, ruthenium red and isopentenyl diphosphate only partly inhibited the responses and TRPV3 silencing was ineffective suggesting remarkable off-target effects of the compounds. Conclusion and Implications: Our results indicate the functional presence of TRPV4 and other thermosensitive TRPV channels in human podocytes and raise the possibility of their involvement in the regulation of glomerular filtration barrier.
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