Role of TRPC6 in Kidney Damage after Acute Ischemic Kidney Injury

Transient receptor potential channel subfamily C, member 6 (TRPC6), a non-selective cation channel
that controls influx of Ca2+
and other monovalent cations into cells, is widely expressed in the kidney.
TRPC6 gene variations have been linked to chronic kidney disease but its role in acute kidney injury
(AKI) is unknown. Here we aimed to investigate the putative role of TRPC6 channels in AKI. We used
Trpc6−/− mice and pharmacological blockade (SH045 and BI-749327), to evaluate short-term AKI
outcomes. Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of
TRPC6 influences the short-term outcomes of AKI. Serum markers, renal expression of epithelial
damage markers, tubular injury, and renal inflammatory response assessed by the histological
analysis were similar in wild-type mice compared to Trpc6−/− mice as well as in vehicle-treated versus
SH045- or BI-749327-treated mice. In addition, we also found no effect of TRPC6 modulation on renal
arterial myogenic tone by using blockers to perfuse isolated kidneys. Therefore, we conclude that
TRPC6 does not play a role in the acute phase of AKI. Our results may have clinical implications for
safety and health of humans with TRPC6 gene variations, with respect to mutated TRPC6 channels in
the response of the kidney to acute ischemic stimuli.