TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?

Abstract

The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca2+ homeostasis and is involved in transcellular Ca2+ reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2 gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care.

Effect of Thymoquinon on TRPM Channels in Rats with Liver Ischemia

“…Studies have increased the possibility of TRP proteins being a new Ca + 2 permeable cation channel. TRP channels either act directly as Ca + 2 entry channels in plasma membranes or they assist in the change in cytosolic free Ca + 2 channels that change the membrane potential, which is the driving force for the modulation of Ca + 2 entry channels (Englisch et al 2022). TRP channels play a role in many important cellular processes such as Ca + 2 -Mg + 2 transmission, regulation of blood pressure, perception of taste, smell, sound, gene expression and secretion, apoptosis, and in many important mechanisms such as the commonly known secondary messenger mechanism, ion entry and exit play.…”

New Insights in the Distribution Profile of TRPC3 and TRPC5 in the Mouse and Human Kidney

“…The Ca 2+ permeable cation-pore arises between the two nal transmembrane segments (S5-S6) of each monomer and its gating activity can be meticulously regulated 2,10 . Due to such properties, TRPC channels are eligible to function as key molecular players in multiple mechanisms including redox-sensitive currents, receptor-operated currents, store-operated currents and more as suggested in non-human experiments 6,9,[11][12][13][14][15] . Diacylglycerol (DAG) is a physiological prominent activator of TRPC3 and TRPC6 but not of TRPC5 7 .…”

“…Until now, most of the scienti c attention was paid to the glomerular localization and function of TRPC channels. However, their relevance in the renal tubular system is increasingly investigated and we recently summarized the current understanding of TRPC3 and TRPC6 11 . Staying with the former, TRPC3 is for instance suggested to be involved in luminal osmosensation and vasopressin-induced aquaporin-2 (AQP-2) translocation in the collecting duct [31][32][33] .…”

“…TRPC channels belong the best studied channels in glomeruli 9 . After a long period of glomerular studies, TRPC6 turned out to be involved in tubular ischemia/reperfusion injuries 11 and in the oncogenesis and tumor progression of renal cell carcinoma 39,40 . As mentioned above, TRPC3 is also increasingly investigated in tubular cells.…”

“…Interestingly, TRPC channels are critical in both glomerular and tubular physiology and pathophysiology as suggested in mostly non-human experiments 1,11,17 . For instance, Staruschenko et al 9 recently summarized the involvement of different channels, including TRPC members, in glomerular function, and both TRPC3 and TRPC5 have been detected in podocytes 9 .…”