Cross-talk between zinc and calcium regulates ion transport: A role for the zinc receptor, ZnR/GPR39

Zinc is essential for many physiological functions, with a major role in digestive system, skin health, and learning and memory. On the cellular level, zinc is involved in cell proliferation and cell death. A selective zinc sensing receptor, ZnR/GPR39 is a Gq-coupled receptor that acts via the inositol trisphosphate pathway to release intracellular Ca²⁺. The ZnR/GPR39 serves as a mediator between extracellular changes in Zn²⁺ concentration and cellular Ca²⁺ signalling. This signalling pathway regulates ion transporters activity and thereby controls the formation of transepithelial gradients or neuronal membrane potential, which play a fundamental role in the physiological function of these tissues. This review focuses on the role of Ca²⁺ signalling, and specifically ZnR/GPR39, with respect to the regulation of the Na⁺/H⁺ exchanger, NHE1, and of the K⁺/Cl⁻ cotransporters, KCC1-3, and also describes the physiological implications of this regulation. (Figure presented.).