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

Although fluctuations in cytosolic Ca 2+ concentration have a crucial role in relaying intracellular messages in the cell 1 , the dynamics of Ca 2+ storage in and release from intracellular sequestering compartments remains poorly understood. The rapid release of stored Ca 2+ requires large concentration gradients that had been thought to result from low-affinity buffering of Ca 2+ by the polyanionic matrices within Ca 2+ -sequestering organelles 2 . However, our results here show that resting luminal free Ca 2+ concentration inside the endoplasmic reticulum and in the mucin granules remains at low levels (20–35 μM). But after stimulation, the free luminal [Ca 2+ ] increases, undergoing large oscillations, leading to corresponding oscillations of Ca 2+ release to the cytosol. These remarkable dynamics of luminal [Ca 2+ ] result from a fast and highly cooperative Ca 2+ /K + ion-exchange process rather than from Ca 2+ transport into the lumen. This common paradigm for Ca 2+ storage and release, found in two different Ca 2+ -sequestering organelles, requires the functional interaction of three molecular components: a polyanionic matrix that functions as a Ca 2+ /K + ion exchanger, and two Ca 2+ -sensitive channels, one to import K + into the Ca 2+ -sequestering compartments, the other to release Ca 2+ to the cytosol.