To a certain extent, all cellular, physiological, and pathological phenomen
a that occur in cells are accompanied by ionic changes. The development of
techniques allowing the measurement of such ion activities has contributed
substantially to our understanding of normal and abnormal cellular function
. Digital video microscopy, confocal laser scanning microscopy, and more re
cently multiphoton microscopy have allowed the precise spatial analysis of
intracellular ion activity at the subcellular level in addition to measurem
ent of its concentration. It is well known that Ca2+ regulates numerous phy
siological cellular phenomena as a second messenger as well as triggering p
athological events such as cell injury and death. A number of methods have
been developed to measure intracellular Ca2+. In this review, we summarize
the advantages and pitfalls of a variety of Ca2+ indicators used in both op
tical and nonoptical techniques employed for measuring intracellular Ca2+ c
oncentration.