Effects of Ca2+ channel antagonist subtypes on mitochondrial Ca2+ transport

Uceda, G.; Garcı́a, Antonio G.; Guantes, J.M.; Michelena, Pedro; Montiel, Carmen

doi:10.1016/0922-4106(95)90170-1

Cited by 20 publications

(10 citation statements)

References 13 publications

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“…In contrast, in rat chromaffin cells, mitochondrial uptake rates are 150-300 fold slower but at [Ca 2+ ] c of only 0.2-2 M, were found [187]. These differences are consistent with dependence of the rate of uptake through the uniporter on the second power of [Ca 2+ ] c [123,124,130,188]. Using mitochondria-targeted aequorin to specifically monitor [Ca 2+ ] M , we found that mitochondria took up about 1100 mol L cells −1 s −1 upon maximal stimulation of Ca 2+ entry into bovine chromaffin cells depolarised with K + [109,124,130]; this value is comparable with the rate of Ca 2+ entry through VDCCs.…”

Section: A Functional Tetrad Shapes Calcium Gradients and Calcium Micsupporting

confidence: 62%

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

et al. 2012

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a b s t r a c tfluxes between the different cell compartments support the proposal that the chromaffin cell has developed functional calcium tetrads formed by calcium channels, cytosolic calcium buffers, the endoplasmic reticulum, and mitochondria nearby the exocytotic plasmalemmal sites. These tetrads shape the Ca 2+ transients occurring during cell activation to regulate early and late steps of exocytosis, and the ensuing endocytotic responses. The different patterns of catecholamine secretion in response to stress may thus depend on such local [Ca 2+ ] c transients occurring at different cell compartments, and generated by redistribution and release of Ca 2+ 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.

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Section: A Functional Tetrad Shapes Calcium Gradients and Calcium Micsupporting

confidence: 62%

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

et al. 2012

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“…This is surprising given the reported low Ca 2+ affinity of the mCUP in BCCs (Uceda et al. ; Montero et al. ).…”

Section: Resultsmentioning

confidence: 91%

“…The simple blockade of one of the two Ca 2+ transporters is insufficient to elevate basal [Ca 2+ ] c ; blockade of both transporters is therefore needed to suppress the mCC and to enhance basal [Ca 2+ ] c . This is surprising given the reported low Ca 2+ affinity of the mCUP in BCCs (Uceda et al 1995;Montero et al 2000). Concerning secretion it is worth mentioning that combined Ru/CGP caused a pronounced increase in peak height; however, it was curious that the initial level of baseline secretion was recovered after each ACh pulse (see in Fig.…”

Section: Effects Of Combined Ru360 and Cgp37157 On [Ca 2+ ] C And Secmentioning

confidence: 92%

Novel features on the regulation by mitochondria of calcium and secretion transients in chromaffin cells challenged with acetylcholine at 37°C

et al. 2013

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From experiments performed at room temperature, we know that the buffering of Ca2+ by mitochondria contributes to the shaping of the bulk cytosolic calcium transient ([Ca2+]c) and secretion transients of chromaffin cells stimulated with depolarizing pulses. We also know that the mitochondrial Ca2+ transporters and the release of catecholamine are faster at 37°C with respect to room temperature. Therefore, we planned this investigation to gain further insight into the contribution of mitochondrial Ca2+ buffering to the shaping of [Ca2+]c and catecholamine release transients, using some novel experimental conditions that have not been yet explored namely: (1) perifusion of bovine chromaffin cells (BCCs) with saline at 37°C and their repeated challenging with the physiological neurotransmitter acetylcholine (ACh); (2) separate blockade of mitochondrial Ca2+ uniporter (mCUP) with Ru360 or the mitochondrial Na+/Ca2+ exchanger (mNCX) with CGP37157; (3) full blockade of the mitochondrial Ca2+ cycling (mCC) by the simultaneous inhibition of the mCUP and the mNCX. Ru360 caused a pronounced delay of [Ca2+]c clearance and augmented secretion. In contrast, CGP37157 only caused a tiny delay of [Ca2+]c clearance and a mild decrease in secretion. The mCC resulting in continued Ca2+ uptake and its release back into the cytosol was interrupted by combined Ru360 + CGP37157 (Ru/CGP), the protonophore carbonyl cyanide‐p‐trifluoromethoxyphenylhydrazone, or combined oligomycin + rotenone (O/R); these three treatments caused a mild but sustained elevation of basal [Ca2+]c that, however, was not accompanied by a parallel increase in basal secretion. Nevertheless, all treatments caused a pronounced augmentation of ACh‐induced secretion, with minor changes of the ACh‐induced [Ca2+]c transients. Combined Ru/CGP did not alter the resting membrane potential in current‐clamped cells. Additionally, Ru/CGP did not increase basal [Ca2+]c near subplasmalemmal sites and caused a mild decrease in the size of the readily releasable vesicle pool. Our results provide new functional features in support of the view that in BCCs there are two subpopulations of mitochondria, M1 underneath the plasmalemma nearby exocytotic sites and M2 at the core cell nearby vesicle transport sites. While M1 serves to shape the ACh‐elicited exocytotic response through its efficient Ca2+ removal by the mCUP, M2 shapes the lower [Ca2+]c elevations required for new vesicle supply to the exocytotic machinery, from the large reserve vesicle pool at the cell core. The mCUP of the M1 pool seems to play a more prominent role in controlling the ACh responses, in comparison with the mNCX.

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“…A proposed sequence for the alteration of Na ϩ and Ca 2ϩ homeostatic mechanisms, leading to death of bovine chromaffin cells incubated with veratridine, and the mechanism of cytoprotection afforded by CGP37157 (CGP). (1) Veratridine delays the inactivation of Na ϩ channels (Ota et al, 1973); (2) enhanced Na ϩ entry through noninactivating Na ϩ channels (Kilpatrick et al, 1982) augments [Na ϩ ] c (3) and causes cell depolarization (4) (Lopez et al, 1995); this leads to cell opening of voltagedependent Ca 2ϩ channels (VDCCs) (5), enhanced Ca 2ϩ entry (6), and [Ca 2ϩ ] c (7) (Maroto et al, 1994(Maroto et al, , 1996Lopez et al, 1995); mitochondria see these enhanced [Ca 2ϩ ] c values and their uniporter augments mitochondrial Ca 2ϩ uptake (8) (Montero et al, 2000) and the [Ca 2ϩ ] m (9) (Montero et al, 2000); augmented [Na ϩ ] c and [Ca 2ϩ ] m increases the activity of the mNCX (10) (Uceda et al, 1995), leading to a more rapid Ca 2ϩ release into the cytosol (11) that contributes to generate larger and longer [Ca 2ϩ ] c oscillations (Maroto et al, 1994(Maroto et al, , 1996Novalbos et al, 1999) and Fig. 3 in this study.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Na⁺/Ca²⁺-Exchanger Blocker CGP37157 Protects against Chromaffin Cell Death Elicited by Veratridine

Nicolau

Diego²,

Cortés³

et al. 2009

J Pharmacol Exp Ther

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Mitochondrial calcium (Ca 2ϩ ) dyshomeostasis constitutes a critical step in the metabolic crossroads leading to cell death. Therefore, we have studied here whether 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157; CGP), a blocker of the mitochondrial Na . This drastic cytoprotective effect of CGP could be explained in part through its regulatory actions on the mNCX.In general, it is accepted that a dysregulation of the mechanism that fine tunes the transient or more sustained levels of the cytosolic Ca 2ϩ concentrations ([Ca 2ϩ ] c ), leads to excitotoxic neuronal death (Schanne et al., 1979) and to neurodegeneration (Mattson, 2007). However, Ca 2ϩ may behave as both a cell survival supporter and a cell death inducer. For instance, cell depolarization and subsequent Ca 2ϩ entry into the cytosol helps to sustain the survival of cerebellar granule cells (Gallo et al., 1987) and bovine chromaffin cells (Orozco et al., 2006). However, chronic elevation of [Ca 2ϩ ] c by ionophores induces apoptosis (Martikainen et al., 1991). The opposite is also true, i.e., Ca 2ϩ antagonists that reduce [Ca 2ϩ ] c also cause neuronal death (Koh and Cotman, 1992) and chromaffin cell death (Novalbos et al., 1999). These apparent contradictory findings may be explained in the frame of the hypothesis suggesting that the [Ca 2ϩ ] c changes occurring during cell activation must move within a critical set point; beyond this point a cytoprotective signal might turn into a cytotoxic one (Koike et al., 1989). In this context, the suggestion of Nicholls (1985) and White and Reynolds (1995) that Ca 2ϩ accumulation into mitochondria could play a neuropro- Article, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.109.154765.ABBREVIATIONS: mNCX, mitochondrial Na ϩ /Ca 2ϩ -exchanger; DMSO, dimethyl sulfoxide; FPL64176, FPL, 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylic acid methyl ester; 30 K ϩ /FPL, 30 mM K ϩ /0.3 M FPL; MTT formazan, 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan, thiazolyl blue formazan; CGP37157, 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one; TTX, tetrodotoxin citrate, octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethan o-10aH- [1,3] dioxocino [6,5-d]pyrimidine

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Effects of Ca2+ channel antagonist subtypes on mitochondrial Ca2+ transport

Cited by 20 publications

References 13 publications

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

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

Novel features on the regulation by mitochondria of calcium and secretion transients in chromaffin cells challenged with acetylcholine at 37°C

Mitochondrial Na⁺/Ca²⁺-Exchanger Blocker CGP37157 Protects against Chromaffin Cell Death Elicited by Veratridine

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Effects of Ca2+ channel antagonist subtypes on mitochondrial Ca2+ transport

Cited by 20 publications

References 13 publications

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

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

Novel features on the regulation by mitochondria of calcium and secretion transients in chromaffin cells challenged with acetylcholine at 37°C

Mitochondrial Na+/Ca2+-Exchanger Blocker CGP37157 Protects against Chromaffin Cell Death Elicited by Veratridine

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Mitochondrial Na⁺/Ca²⁺-Exchanger Blocker CGP37157 Protects against Chromaffin Cell Death Elicited by Veratridine