Role of Ca²⁺/K⁺ ion exchange in intracellular storage and release of Ca²⁺

Although fluctuations in cytosolic Ca²⁺ concentration have a crucial role in relaying intracellular messages in the cell, the dynamics of Ca²⁺ storage and release from intracellular sequestering compartments remains poorly understood. The rapid release of stored Ca²⁺ requires large concentration gradients that had been thought to result from low-affinity buffering of Ca²⁺ by the polyanionic matrices within Ca²⁺-sequestering organelles. However, our results here show that resting luminal free Ca²⁺ concentration inside the endoplasmic reticulum and in the mucin granules remains at low levels (20-35 μM). But after stimulation, the free luminal [Ca²⁺] increases, undergoing large oscillations, leading to corresponding oscillations of Ca²⁺ release to the cytosol. Therse remarkable dynamics of luminal [Ca²⁺] result from a fast and highly cooperative Ca²⁺/K⁺ ion- exchange process rather than from Ca²⁺ transport into the lumen. This common paradigm for Ca²⁺ storage and release, found in two different Ca²⁺-sequestering organelles, requires the functional interaction of three molecular components: a polyanionic matrix that functions as a Ca²⁺/K⁺ ion exchanger, and two Ca²⁺-sensitive channels, one to import K⁺ into the Ca²⁺-sequestering compartments, the other to release Ca²⁺ to the cytosol.