The renal connecting tubule: Resolved and unresolved issues in Ca2+ transport

The renal connecting tubule (CNT) localizes to the distal part of the nephron between the distal convoluted tubule and the collecting duct, and consists of two different cell types: segment-specific and intercalated cells. The former reabsorb water (H2O), sodium (Na+) and calcium (Ca2+) ions to the blood compartment, while secreting potassium ions (K+) into the pro-urine. The latter cells contribute to the renal control of the acid-base balance. Several factors and hormones tightly regulate these transport processes. Although the CNT reabsorbs only ∼15% of filtered Ca2+ load, this segment is finally decisive for the amount of Ca2+ that appears in the urine. Impaired Ca2+ transport across CNT can provoke severe urinary Ca2+ excretion, called hypercalciuria. This review mainly focuses on the activity, abundance and expression of the epithelial Ca2+ channel named Transient Receptor Potential Vanilloid 5 (TRPV5) that is the gatekeeper of active Ca2+ reabsorption in the CNT.