In his introductory remarks to open the symposium “New Optical Methods in Cell Physiology,” held in Woods Hole, MA, September 9–11, 1999, Brian Salzberg noted that 15 years of technological innovation had intervened since the Society of General Physiologists had held its first symposium on this topic, entitled simply “Optical Methods in Cell Physiology” (organized by Paul De Weer and Brian M. Salzberg). That first meeting highlighted work with voltage-sensitive dyes (enabling noninvasive recording of electrical activity in cells, or groups of cells), and with photolabile (e.g., caged) compounds (permitting sudden release of, say, ATP or Ca2+), and featured the introduction of the highly successful ratiometric fluorescent indicators, Fura-2 and Indo-1, which opened the door to routine measurement of the transient changes in intracellular [Ca2+] that underlie so many facets of cellular signal transduction. The...

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