Calcium Entry, Calcium Redistribution, and Exocytosis

• Published in: Annals of the New York Academy of Sciences Vol. 971; no. 1; pp. 108 - 116
• Main Authors: CUCHILLO-IBÁÑEZ, INMACULADA, ALBILLOS, ALMUDENA, ALDEA, MARCOS, ARROYO, GLORIA, FUENTEALBA, JORGE, GARCÍA, ANTONIO G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2002
• Subjects: Animals; Binding Sites; Caffeine - pharmacology; Calcium - metabolism; calcium signal; Catecholamines - metabolism; Cattle; chromaffin cell; Chromaffin Cells - metabolism; Cytoskeleton; Endoplasmic Reticulum - metabolism; Exocytosis; Humans; Kinetics; Models, Biological; Potassium - metabolism; Potassium - pharmacology; Protein Structure, Tertiary
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2002.tb04444.x

: At a given cytosolic domain of a chromaffin cell, the rate and amplitude of the Ca2+ concentration, [Ca2+]c, depend on at least three efficient regulatory mechanisms: (1) the plasmalemmal Ca2+ channels; (2) the endoplasmic reticulum (ER); and (3) the mitochondria. High‐voltage activated Ca2+ channels of the L, N, P/Q, and R subtypes are expressed with different densities in various mammalian species; they are regulated by G proteins coupled to purinergic and opiate receptors, as well as by voltage and the local changes of [Ca2+]c. Targeted aequorin and confocal microscopy show that Ca2+ entry through Ca2+ channels can refill the ER to near millimolar concentrations and causes the release of ER Ca2+ (CICR). We have also seen that, depending on its degree of filling, the ER may act as a sink or source of Ca2+ that modulates the release of catecholamine. Targeted aequorins with different Ca2+ affinities show that mitochondria undergo surprisingly rapid millimolar Ca2+ transients ([Ca2+]M) upon stimulation of chromaffin cells with ACh, high K+, or caffeine. Physiological stimuli generate [Ca2+]c microdomains at these functional complexes in which the local subplasmalemmal [Ca2+]c rises abruptly from 0.1 μM to about 50 μM. This triggers CICR, mitochondrial Ca2+ uptake, and exocytosis in nearby secretory active sites. That this is true is shown by the observation that protonophores abolish mitochondrial Ca2+ uptake and drastically increase catecholamine release by 3‐ to 5‐fold. This increase is likely due to acceleration of vesicle transport from a reserve pool to a ready‐release vesicle pool; such transport might be controlled by Ca2+ redistribution to the cytoskeleton, through CICR and/or mitochondrial Ca2+ release.