Intercalated Cells of the Kidney Collecting Duct in Kidney Physiology

The epithelium of the kidney collecting duct (CD) is composed mainly of two different types of cells with distinct and complementary functions. CD principal cells traditionally have been considered to have a major role in Na⁺ and water regulation, while intercalated cells (ICs) were thought to largely modulate acid-base homeostasis. In recent years, our understanding of IC function has improved significantly owing to new research findings. Thus, we now have a new model for CD transport that integrates mechanisms of salt and water reabsorption, K⁺ homeostasis, and acid-base status between principal cells and ICs. There are three main types of ICs (type A, type B, and non-A, non-B), which first appear in the late distal convoluted tubule or in the connecting segment in a species-dependent manner. ICs can be detected in CD from cortex to the initial part of the inner medulla, although some transport proteins that are key components of ICs also are present in medullary CD, cells considered inner medullary. Of the three types of ICs, each has a distinct morphology and expresses different complements of membrane transport proteins that translate into very different functions in homeostasis and contributions to CD luminal pro-urine composition. This review includes recent discoveries in IC intracellular and paracrine signaling that contributes to acid-base regulation as well as Na⁺, Cl^-, K⁺, and Ca²⁺ homeostasis. Thus, these new findings highlight the potential role of ICs as targets for potential hypertension treatments.