Measuring calcium signals and exocytosis in tissues

BackgroundSince the 1960s it has been clear that calcium is a key regulator of exocytosis. Early experiments directly showed that the secretory output was calcium dependent. But it has taken improvements in technology and clever experimentation to determine the relationships between the calcium signal and exocytosis. Today controversies still remain because of limitations in our ability to record both the calcium responses within the local domains that control secretion and in the methods used to record exocytosis.Scope of reviewHere the techniques used to measure calcium and exocytosis are reviewed with a distinction being drawn between measurements in excitable cells versus measurements in non-excitable cells. The review has a focus on techniques that are relevant to in vitro studies of native tissues and recent in vivo recordings.Major conclusionsThere are a range of methods used to study the stimulus-secretion pathway. Each presents their own advantages and drawbacks. These are discussed with reference to the latest work determining the factors controlling exocytosis in tissues.General significanceStimulus-secretion coupling is the fundamental step in the control of neurotransmitter release, hormone secretion and protein secretion. Understanding secretory control is therefore important in understanding the physiological regulation of processes ranging from learning and memory to pancreatic secretion. Recent technological advances are now enabling us to study stimulus-secretion coupling within native tissues. This is helping us to understand the physiological complexities of secretory control. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signalling.

► Discussion of spatio-temporal control of exocytosis by calcium.
► Methods to determine and manipulate cytosolic calcium in the cell.
► Methods to assay exocytosis and determine secretory output.
► Distinctions in secretion between excitable and non-excitable cells.