Na+/Ca2+exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca2+via ER nanojunctions in vascular endothelial cells

Giuro, Cristiana Maria Loredana Di; Shrestha, Niroj; Malli, Roland; Breemen, Cornelis van; Fameli, Nicola

doi:10.1101/084285

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…The present study shows for the rst time that the "Ca 2+ in ux" mode NCX participates in the maintenance of the myogenic tone of isolated middle cerebral artery, since administration of NCX inhibitor -KB-R7943 resulted in the dilation of this vessel under basal conditions. This inhibitor of NCX, at a dose of 10 µmol L − 1 used in our study, selectively inhibits the Ca 2+ entry mode of the exchanger [31][32][33][34].…”

Section: Discussionmentioning

confidence: 91%

“…This dose of KB-R7943 has been used to inhibit Ca 2+ -entry mode of Na + /Ca 2+ exchanger in the endothelial cells. 32,33 In series VII, nimodipine (100 nmol L -1 ) -the antagonist of L-type Ca 2+ membrane channels of vascular smooth muscle, was administered to the buffer prior to the lowering of sodium concentration. This experiment was designed to test whether relaxation of the wall of the MCA prior to the application of low sodium buffer affects vasodilatory capacity of the vessel.…”

Section: Experimental Protocolmentioning

confidence: 99%

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Role of the endothelial reverse mode sodium-calcium exchanger in the dilation of the rat middle cerebral artery during hypoosmotic hyponatremia

Klapczyńska

Aleksandrowicz

Koźniewska

2022

Preprint

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The decrease in serum sodium ions concentration below 135 mmol L− 1 is usually accompanied by a decrease in plasma osmolality (hypoosmotic hyponatremia) and leads to the disorder of intracranial homeostasis mainly due to the cellular swelling. Recently, using in vitro model of hypoosmotic hyponatremia, we have found that a decrease in sodium ions concentration in the perfusate to 121 mmol L− 1 relaxes the isolated rat middle cerebral artery (MCA). The aim of present study was to explore the mechanism responsible for this relaxation. Isolated, pressurized and perfused MCAs placed in a vessel chamber were subjected to a decrease of sodium ions concentration to 121 mmol L− 1. The changes in the diameter of the vessels were monitored with a video camera. The removal of the endothelium, inhibition of nitric oxide-dependent signaling or reverse mode sodium-calcium exchanger (NCX) were used to study the mechanism of the dilation of the vessel during hyponatremia. The dilation of the MCA (19 ± 5%, p < 0.005) in low sodium buffer was absent after removal of the endothelium or administration of the inhibitor of the reverse mode of sodium-calcium exchange, and was reversed to constriction after the inhibition of nitric oxide (NO)/cGMP signaling. The dilation of the middle cerebral artery of the rat in 121 mM Na+ buffer depends on the endothelium, NO signaling and reverse mode of sodium-calcium exchange. Hyponatremia may constrict large cerebral arteries with impaired NO-dependent signaling and add to vascular spasm such as the one observed in the late phase after subarachnoid hemorrhage.

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Section: Discussionmentioning

confidence: 91%

Section: Experimental Protocolmentioning

confidence: 99%

Role of the endothelial reverse mode sodium-calcium exchanger in the dilation of the rat middle cerebral artery during hypoosmotic hyponatremia

Klapczyńska

Aleksandrowicz

Koźniewska

2022

Preprint

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Tissue Specificity: The Role of Organellar Membrane Nanojunctions in Smooth Muscle Ca2+ Signaling

Fameli

Evans

Breemen

2017

Store-Operated Ca²⁺ Entry (SOCE) Pathways

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In this chapter we examine the importance of cytoplasmic nanojunctions-nanometer scale appositions between organellar membranes including the molecular transporters therein-to the cell signaling machinery, with specific reference to Ca transport and signaling in vascular smooth muscle and endothelial cells. More specifically, we will consider the extent to which quantitative modeling may aid in the development of our understanding of these processes. Testament to the requirement for such approaches lies in the fact that recent studies have provided evermore convincing evidence in support of the view that cytoplasmic nanospaces may be as significant to the process of Ca signaling as the Ca transporters, release channels, and Ca-storing organelles themselves. Moreover, the disruption and/or dysfunction of cytoplasmic nanospaces may be central to the origin of certain diseases. By way of introduction, we provide a historical perspective on the identification of smooth muscle cell plasma membrane (PM)-sarcoplasmic reticulum (SR) nanospaces and the early evidence in support of their role in the generation of asynchronous Ca waves. We then summarize how stochastic modeling approaches can aid and guide the development of our understanding of two basic functional steps leading to healthy smooth muscle cell contraction. We furthermore outline how more sophisticated and realistic quantitative stochastic modeling may be employed not only to test working hypotheses, but also to lead in their development in a manner that informs further experimental investigation. Finally, we consider more recently defined nanospaces such as the lysosome-SR junction, by way of demonstrating the importance of quantitative stochastic modeling to our understanding of signaling mechanisms.

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Cardiovascular and Hemostatic Disorders: SOCE in Cardiovascular Cells: Emerging Targets for Therapeutic Intervention

Shrestha

Fameli

2017

Store-Operated Ca²⁺ Entry (SOCE) Pathways

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The discovery of the store-operated Ca entry (SOCE) phenomenon is tightly associated with its recognition as a pathway of high (patho)physiological significance in the cardiovascular system. Early on, SOCE has been investigated primarily in non-excitable cell types, and the vascular endothelium received particular attention, while a role of SOCE in excitable cells, specifically cardiac myocytes and pacemakers, was initially ignored and remains largely enigmatic even to date. With the recent gain in knowledge on the molecular components of SOCE as well as their cellular organization within nanodomains, potential tissue/cell type-dependent heterogeneity of the SOCE machinery along with high specificity of linkage to downstream signaling pathways emerged for cardiovascular cells. The basis of precise decoding of cellular Ca signals was recently uncovered to involve correct spatiotemporal organization of signaling components, and even minor disturbances in these assemblies trigger cardiovascular pathologies. With this chapter, we wish to provide an overview on current concepts of cellular organization of SOCE signaling complexes in cardiovascular cells with particular focus on the spatiotemporal aspects of coupling to downstream signaling and the potential disturbance of these mechanisms by pathogenic factors. The significance of these mechanistic concepts for the development of novel therapeutic strategies will be discussed.

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Na⁺/Ca²⁺exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca²⁺via ER nanojunctions in vascular endothelial cells

Cited by 3 publications

References 51 publications

Role of the endothelial reverse mode sodium-calcium exchanger in the dilation of the rat middle cerebral artery during hypoosmotic hyponatremia

Role of the endothelial reverse mode sodium-calcium exchanger in the dilation of the rat middle cerebral artery during hypoosmotic hyponatremia

Tissue Specificity: The Role of Organellar Membrane Nanojunctions in Smooth Muscle Ca2+ Signaling

Cardiovascular and Hemostatic Disorders: SOCE in Cardiovascular Cells: Emerging Targets for Therapeutic Intervention

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