Calcium ions (Ca 2+ ) play critical roles in various biological phenomena. The free Ca 2+ concentration in the cytoplasm of a resting cell is at the 10 -7 M level, whereas that outside the cell is 10 -3 M, creating a 10,000-fold gradient of Ca 2+ concentrations across the cell membrane, separating the intracellular and extracellular solutions. 1),2) When a cell is activated by external stimuli, the intracellular Ca 2+ concentration increases to levels of 10 -6 -10 -5 M through Ca 2+ entry from the extracellular solution via plasma membrane Ca 2+ channels and/or Ca 2+ release from intracellular stores. This transient increase in Ca 2+ functions as an important signal mediated by Ca 2+ sensors. Thus, Ca 2+ signals are transmitted to intracellular loci such as distinct, localized targets of Ca 2+ sensors. Among numerous Ca 2+ sensors present in cells, calmodulin is a highly conserved and ubiquitous Ca 2+ sensor. 3) .