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Calcium Signaling and Exocytosis in Adrenal Chromaffin Cells
Abstract
At a given cytosolic domain of a chromaffin cell, the rate and amplitude of the Ca2+ concentration ([Ca2+]c) depends on at least four efficient regulatory systems: 1) plasmalemmal calcium channels, 2) endoplasmic reticulum, 3) mitochondria, and 4) chromaffin vesicles. Different mammalian species express different levels of the L, N, P/Q, and R subtypes of high-voltage-activated calcium channels; in bovine and humans, P/Q channels predominate, whereas in felines and murine species, L-type channels predominate. The calcium channels in chromaffin cells are regulated by G proteins coupled to purinergic and opiate receptors, as well as by voltage and the local changes of [Ca2+]c. Chromaffin cells have been particularly useful in studying calcium channel current autoregulation by materials coreleased with catecholamines, such as ATP and opiates. Depending on the preparation (cultured cells, adrenal slices) and the stimulation pattern (action potentials, depolarizing pulses, high K+, acetylcholine), the role of each calcium channel in controlling catecholamine release can change drastically. Targeted aequorin and confocal microscopy shows that Ca2+ entry through calcium channels can refill the endoplasmic reticulum (ER) to nearly millimolar concentrations, and causes the release of Ca2+ (CICR). Depending on its degree of filling, the ER may act as a sink or source of Ca2+ that modulates catecholamine release. Targeted aequorins with different Ca2+ affinities show that mitochondria undergo surprisingly rapid millimolar Ca2+ transients, upon stimulation of chromaffin cells with ACh, high K+, or caffeine. Physiological stimuli generate [Ca2+]c microdomains in which the local subplasmalemmal [Ca2+]c rises abruptly from 0.1 to approximately 50 microM, triggering CICR, mitochondrial Ca2+ uptake, and exocytosis at nearby secretory active sites. The fact that protonophores abolish mitochondrial Ca2+ uptake, and increase catecholamine release three- to fivefold, support the earlier observation. This increase is probably due to acceleration of vesicle transport from a reserve pool to a ready-release vesicle pool; this transport might be controlled by Ca2+ redistribution to the cytoskeleton, through CICR, and/or mitochondrial Ca2+ release. We propose that chromaffin cells have developed functional triads that are formed by calcium channels, the ER, and the mitochondria and locally control the [Ca2+]c that regulate the early and late steps of exocytosis.
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“Single-cell amperometry measures the numbers of released catecholamine molecules during every individual exocytosis event (Garcia et al., 2006; Wightman et al., 1991).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Garcia et al., 2006
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Self-citation
Metadata
- Authors
- García, A. G., García-De-Diego, A. M., Gandía, L., Borges, R., & García-Sancho, J.
- ORCID
- Borges, Ricardo
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2006-10
- Volume
- 86
- Issue
- 4
- Pages
- 1093-1131
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2137229430
- Cited by
- 349
- References
- 426
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 14 · 2023: 10 · 2022: 22 · 2021: 9 · 2020: 15 · 2019: 13 · 2018: 16 · 2017: 22 · 2016: 11 · 2015: 12 · 2014: 18 · 2013: 19 · 2012: 23
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- calcium signaling, exocytosis, catecholamine release, calcium channels, P/Q-type calcium channels, L-type calcium channels, calcium-induced calcium release, endoplasmic reticulum, mitochondrial calcium uptake, chromaffin granules, opioid receptors, purinergic receptors, G proteins, aequorin, vesicle trafficking, cytoskeleton, adrenal medulla, confocal microscopy
- MeSH terms
- Adrenal Glands, Animals, Exocytosis, Humans, Chromaffin Cells, Calcium Signaling
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