Die Rolle des TRPC6 Kanals im Rahmen der akuten Nierenschädigung

Aims: Transient receptor potential (TRP) channels are non-selective cation channels that promote influx of Ca2+, Mg2+ and monovalent cations into cells. TRP channel subfamily C, member 6 (TRPC6) is widely expressed - next to several other tissues - in the kidney, and gene variations were linked to fibrosing renal disease. Here we aimed to investigate the putative role of TRPC6 channels in acute kidney injury (AKI). Since ischemia/reperfusion injury is known relate to Ca2+ overload, we hypothesized that inhibition of TRPC6 ameliorates AKI.
Methods: We used Trpc6-/- mice and SH045, a pharmacological inhibitor of TRPC6, to evaluate short-term AKI outcomes. Ischemia was induced after right–sided nephrectomy by clipping the renal pedicle of the left kidney for 20 or 17.5 minutes. SH045 was used for intravenous injection (2 mg/kg) 30 minutes before I/R surgery in the pharmacological studies with WT mice.
Results: Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influence the short-term outcomes of AKI. Blood markers (Creatinine in WT [131.4±33.3 µmol/l] vs Trpc6-/- [159.6±41.7 µmol/l] mice after 24 hours of reperfusion and in the pharmacological study: 17.5 min-I/R vehicle [199.5±21.8 µmol/l] versus 17.5 min-I/R SH045 [172.6±31.6 µmol/l], and 20 min-I/R vehicle [212.2±8.4 µmol/l] versus 20 min-I/R SH045 [226.2±28.6 µmol/l], all comparisons are n.s.), renal expression of epithelial damage markers, tubular injury and renal inflammatory response assessed by histological analysis were similar in wild-type mice compared to Trpc6-/- mice as well as in vehicle-treated versus SH045-treated mice. In addition, our results also found no effect of TRPC6 modulation on renal myogenic tone by using SH045 to perfuse isolated kidneys.
Conclusion: Therefore, we conclude that TRPC6 does not play role on the acute phase of AKI. Further studies should focus if TRPC6 inhibition could be protective in terms of long-term outcome of an AKI.