Nate Hellman’s bench was three benches down from my lab. Nate and I trained together as clinical fellows. He and I had also brainstormed on research projects involving TRP channels and kidney disease. TRP channels are my research area of interest. It therefore seems appropriate to discuss some aspects of what Nate and I jokingly referred to as our “covert” project in my first blog posting.
What are TRP channels? And why do they matter in terms of kidney health and disease?
TRP stands for Transient Receptor Potential, a large family of non-selective cationic channels with diverse tissue distribution and diverse cellular functions. They were initially discovered in Drosophila (fruit fly) photoreceptors where they mediate fly vision. Some refer to them as “the last bastion of ion channels” since there is still much we do not understand about their role in health and disease. There are a few TRP subfamilies, indicated by letters which are there for various historical reasons (a discussion for another day – just take my word for it for now, or refer to a review by Ramsey et al., Annu Rev Physiol. 2006;68:619-47), but there are the TRPCs, the TRPVs, the TRPMs, the TRPPs, the TRPMLs and the TRPAs.
A few fun facts:
- TRP channels (TRPV1) are responsible for the hot taste of chili peppers in your mouth.
- TRP channels (TRPM8) also give you the cold sensation of menthol.
But how are TRP channels pertinent to your kidneys? It turns out that they are actually involved in many aspects of kidney physiology and disease (called “channelopathies”):
We’ll start from my favorite: Proteinuric kidney disease. Mutations in TRPC6 were found in a number of families with adult onset Focal Segmental Glomerulosclerosis. Many of us are now actively involved in research to identify the precise mechanisms by which disease occurs in these patients, but deleterious effects due to channel mutations in glomerular podocytes are strongly suspected.
Another channel, TRPV5, mediates vitamin D dependent calcium uptake in tubular epithelial cells. The absence of TRPV5 channels (at least in mice) causes renal calcium wasting and bone loss.
Perhaps more intriguingly, mutations in TRPM6 have been implicated in human hypomagnesemia with secondary hypocalcemia (HGH) as this channel is involved in renal magnesium uptake.
And rather famously, of course, polycystic kidney disease (ADPKD) emerges due to mutations in two slightly more distant relatives in the TRP family, the polycystins, known as TRPP1 and TRPP2.
This of course brings us full circle back to Nate and his research, which was focused on cystic disease, and specifically cystic kidney disease.
As this is my first time blogging, please let me know what you think, your comments and suggestions are welcome!