Cytosolic organelles shape calcium signals and exo–endocytotic responses of chromaffin cells

The concept of stimulus–secretion coupling was born from experiments performed in chromaffincells 50 years ago. Stimulation of these cells with acetylcholine enhances calcium (Ca2+) entry and this generates a transient elevation of the cytosolic Ca2+ concentration ([Ca2+]c) that triggers the exocytotic release of catecholamines. The control of the [Ca2+]csignal is complex and depends on various classes of plasmalemmal calcium channels, cytosoliccalcium buffers, the uptake and release of Ca2+ from cytoplasmic organelles, such as the endoplasmic reticulum, mitochondria, chromaffin vesicles and the nucleus, and Ca2+ extrusion mechanisms, such as the plasma membrane Ca2+-stimulated ATPase, and the Na+/Ca2+ exchanger. Computation of the rates of Ca2+ fluxes between the different cell compartments support the proposal that the chromaffincell has developed functional calcium tetrads formed by calcium channels, cytosoliccalcium buffers, the endoplasmic reticulum, and mitochondria nearby the exocytotic plasmalemmal sites. These tetrads shape the Ca2+ transients occurring during cell activation to regulate early and late steps of exocytosis, and the ensuing endocytoticresponses. The different patterns of catecholamine secretion in response to stress may thus depend on such local [Ca2+]c transients occurring at different cell compartments, and generated by redistribution and release of Ca2+ by cytoplasmic organelles. In this manner, the calcium tetrads serve to couple the variable energy demands due to exo–endocytotic activities with energy production and protein synthesis.
The work of the author’s laboratories has been supported by the following institutions. To AGG: (1) SAF2010-21795, Ministerio de Ciencia e Innovación (MCINN); (2) RETICS RD06/0009, Instituto de Salud Carlos III (MICINN); (3) S-SAL-0275-2006, Comunidad Autónoma de Madrid; (4) NDG07/9 y NDG09/8, Agencia Laín Entralgo, Comunidad Autónoma de Madrid, Spain. (5) Fundación Teófilo Hernando. To JGS: grants from the EU-ERA-Net programme, the Spanish Ministerio de Ciencia e Innovación (MICINN; SAF2008- 03175-E and BFU2010-17379), the Instituto de Salud Carlos III (RD06/0010/0000) and the Junta de Castilla y León (gr175).