Fig. 7.

Proposed role of transient receptor potential vanilloid type 4 (TRPV4) in the regulation of H⁺-K⁺-ATPase-dependent K⁺ reabsorption in the collecting duct (CD) during regular and K⁺-deficient states. Larger icon sizes reflect higher expression levels of transport proteins. During the regular K⁺ diet (left), TRPV4 has no appreciable role in the regulation of CD K⁺ reabsorption. Tubular flow is not elevated, and the activity of TRPV4 channels is at a baseline. H⁺-K⁺-ATPase expression is also low. The CD secretes K⁺ due to the activity of the Ca²⁺-independent renal outer medullary K⁺(ROMK) channel in principal cells. In the K⁺-deficient state (right), there is virtually no ROMK expression, whereas H⁺-K⁺-ATPase levels are upregulated. Activation of TRPV4 by high tubular flow inhibits H⁺-K⁺-ATPase activity in both principal and intercalated cells to decrease/shape K⁺ reabsorption in the CD. While intercalated cells account for only ~25% of total CD cells, the activity of H⁺-K⁺-ATPase is nearly 10-fold higher in intercalated cells compared with principal cells (see Fig. 6B). Overall, the total contribution of H⁺-K⁺-ATPase activity would be still roughly three times higher in intercalated cells, even after correction for cell numbers. [Ca²⁺]_i, intracellular Ca²⁺ concentration.