Supralinear Ca2+ signaling by cooperative and mobile Ca2+ buffering in Purkinje neurons

Endogenous high-affinity Ca2+ buffering and its roles were investigated in mouse cerebellar Purkinje cells with the use of a low-affinity Ca2+ indicat or and a high-affinity caged Ca2+ compound. Increases in the cytosolic Ca2 concentration ([Ca2+](i)) were markedly facilitated during repetitive depo larization, resulting in the generation of steep micromolar Ca2+ gradients along dendrites. Such supralinear Ca2+ responses were attributed to the sat uration of a large concentration (0.36 mM) of a mobile, high-affinity (diss ociation constant, 0.37 mu M) Ca2+ buffer with cooperative Ca2+ binding sit es, resembling calbindin-D-28K, and to an immobile, low-affinity Ca2+ buffe r. These data suggest that the high-affinity Ca2+ buffer operates as the ne uronal computational element that enables efficient coincidence detection o f the Ca2+ signal and that facilitates spatiotemporal integration of the Ca 2+ signal at submicromolar [Ca2+](i).