Reversible interruption of ER Ca 2+ uptake inversely affects ACh-elicited exocytosis in mouse and bovine chromaffin cell
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COMMENTARY
Reversible interruption of ER Ca2+ uptake inversely affects ACh-elicited exocytosis in mouse and bovine chromaffin cells Arturo Hernández-Cruz 1 Received: 14 October 2020 / Revised: 14 October 2020 / Accepted: 20 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Adrenal medulla chromaffin cells (CCs) are invaluable cell models for neurosecretion studies [5]. Significant differences in Ca2+ dynamics and exocytosis exist in CCs from several mammalian species (bovine, rat, guinea pig, cat, human) [7]. Nonetheless, the interest in mouse CCs (MCCs) increased disproportionally after the advent of transgenic mouse models to explore, from the complexities of Ca2+ signaling and exocytosis to alterations of Ca2+ homeostasis in neurodegenerative diseases [5]. There is a consensus that bovine chromaffin cells (BCCs) express an efficient mechanism of [Ca2+]i signal amplification by which the initial [Ca2+]i elevation opens ryanodine receptors (RyRs) from the ER through which Ca2+ is released into the cytosol [2, 8]. An influential article [10] reported that MCCs lack RyR-mediated Ca 2+ -induced Ca 2+ release (CICR), but two recent studies in CCs from C57BL/6 mice [4, 11] conclusively support the presence of RyR and CICR. A differential role of mitochondria Ca2+ handling has also been reported: They sequester a more significant fraction of Ca2+ influx in MCCs than in BCCs [1]. Martínez-Ramírez et al., in this issue [9], compare the effects of acute, reversible SERCA pump inhibition by ciclopiazonic acid (CPA) on exocytotic responses and intracellular Ca2+ signals elicited by application to MCCs or BCCs of short ACh pulses at different intervals and extracellular [Ca2+]. The results could not be more contrasting: enhancement of exocytosis during CPA treatment and inhibition of exocytosis upon CPA washout in MCCs; inhibition of This article is a commentary to the original article https://doi.org/10.1007/ s00424-020-02483-1 * Arturo Hernández-Cruz [email protected] 1
Instituto de Fisiología Celular, Departamento de Neurociencia Cognitiva and Laboratorio Nacional de Canalopatías, Universidad Nacional Autónoma de México, CP 04510 México City CDMX, México
exocytosis during CPA exposure, and rebound exocytosis recovery upon CPA washout in BCCs. These differences, found under identical recording conditions at 37 °C, appear genuine. Intriguingly, CPA only reduced ACh-induced Ca2+ signals slightly in both cell types. Why the reversible pharmacological inhibition of ER Ca2+ uptake affects so differently ACh-elicited CA exocytosis in MCCs and BCCs? The authors suggest that the opposite effects of CPA on ACh-induced exocytosis in MCCs and BCCs result from different [Ca2+]i handling by the ER and mitochondria, affecting vesicle traffic and refilling of the rapid release pool. During the SERCA’s acute blockade, more Ca2+ is diverted to and taken up by the mitochondria through their Ca2+ uniporter. Conversely, upon restoration of ER Ca2+ uptake, mitochondria release Ca2+ through the Na+/Ca2+ exchanger, wh
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