Functionally and spatially distinct Ca2+ stores are revealed in cultured vascular smooth muscle cells.

Tribe, Rachel M.; Borin, M. L.; Blaustein, Mordecai P.

doi:10.1073/pnas.91.13.5908

Cited by 93 publications

(73 citation statements)

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“…If both receptors exist on a single store, Ca 2ϩ release from each receptor should be equally sensitive to the inhibitors. Differences in the sensitivity of caffeine and IP 3 -mediated Ca 2ϩ release to pump inhibitors has been interpreted as evidence of the existence of separate stores for each receptor (22,29,30). For example, the ryanodine/caffeine-sensitive store was not sensitive to thapsigargin or cyclopiazonic acid, whereas the IP 3 -sensitive Ca 2ϩ store was depleted by the Ca 2ϩ pump inhibitors in arterial myocytes (22,30).…”

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confidence: 99%

A Single Luminally Continuous Sarcoplasmic Reticulum with Apparently Separate Ca2+ Stores in Smooth Muscle

McCarron

Olson

2008

Journal of Biological Chemistry

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In smooth muscle, the endoplasmic reticulum (ER) 2 exists as an extensive membrane network of tubules, flattened cisternae, and vesicles (1, 2) to comprise rough (RER, which carries ribosomes) and smooth (SER) reticula. RER predominates around the nucleus and is scattered throughout the cytoplasm and appears to be in luminal continuity with the SER (1, 3, 4). SER is found mainly near the cell surface to run in close apposition to the plasma membrane. In various tissues, changes in ER structure may occur at different developmental stages and when the cells experience prolonged activation (reviewed in Ref. 5). These changes may give the impression of a labile (pleiomorphic) ER network capable of modifications in structure and, consequently, function.The Ca 2ϩ storage element of the ER, the sarcoplasmic reticulum (SR), may be a specialized region of the SER that is endowed with those proteins responsible for the uptake (Ca 2ϩ pumps), storage (calsequestrin), and release ryanodine receptor ((RyR) and inositol 1,4,5-trisphosphate receptor (IP 3 R)) of Ca 2ϩ (4, 6). The SR, by regulating the cytoplasmic Ca 2ϩ concentration ([Ca 2ϩ ] c ), plays a central role in Ca 2ϩ signaling to contribute to activities such as gene expression, growth, contraction, and cell death (reviewed in Refs. 7-10). In determining the qualitative nature of the biological response, the structural arrangement of the SR through the cell may be instrumental in enabling different functions to occur and proceed from various regions of the cell. For example, the SR, as a series of multiple, separate Ca 2ϩ -storage elements, each with their own limited measure of Ca 2ϩ , may explain localized all-or-none responses in restricted regions of the cell, the graded release of Ca 2ϩ from the SR in the "quantal" release process and the various sensitivities to IP 3 measured throughout the cell (11-15). Yet, whether or not the SR exists as multiple separate Ca 2ϩ storage units or as a single luminally continuous entity in which Ca 2ϩ diffuses freely throughout, is unclear.Evidence for the existence of multiple Ca 2ϩ storage units comes from the heterogeneity of the SR in its Ca 2ϩ handling capacity in smooth muscle (1, 4, 16). The SR near the center of the cells may be depleted less readily of its Ca 2ϩ than that of peripherally located SR (1) and x-ray microprobe analysis revealed Ca 2ϩ -rich spots in the central and peripheral SR in portal vein and taenia coli (17, 18). Calsequestrin was not uniformly distributed through the SR network but clustered preferentially at sites most often within the peripheral SR (4). These calsequestrin-rich elements of the SR were also enriched with IP 3 R (4). This evidence provides a morphological basis for the existence of various arrangements of Ca 2ϩ release channels. The SR Ca 2ϩ stores have been classified on the basis of the arrangement of IP 3 R and RyR and conflicting evidence exists regarding their number and receptor arrangement. To determine the organization of the SR Ca 2ϩ stores, in native cells, the predominant...

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confidence: 99%

A Single Luminally Continuous Sarcoplasmic Reticulum with Apparently Separate Ca2+ Stores in Smooth Muscle

McCarron

Olson

2008

Journal of Biological Chemistry

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“…Stores have also been differentiated by their sensitivity to the SERCA pump inhibitors cyclopiazonic acid (CPA) and thapsigargin. In A7r5 cells (a cell line derived from thoracic aorta tissue) there are stores containing RyR that are insensitive to thapsigargin and separate stores in the same cells (also with RyR) that are sensitive to thapsigargin [12]. In an alternative proposal for store arrangement in A7r5 cells, a thapsigargin-insensitive store with IP 3 R but not RyR may exist [36].…”

Section: Structure Of the Ca 2+ Storesmentioning

confidence: 99%

“…11.2) [e.g. 7,[10][11][12]. Although the structure is unresolved, the arrangement of the store is proposed to account for several characteristics of Ca 2+…”

Section: Physiological Functions Proposed To Be Explained By the Strumentioning

confidence: 99%

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Calcium Mobilization via Intracellular Ion Channels, Store Organization and Mitochondria in Smooth Muscle

McCarron

Chalmers

Wilson

et al. 2016

Vascular Ion Channels in Physiology and Disease

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This version is available at https://strathprints.strath.ac.uk/55095/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. Abstract In smooth muscle, Ca 2+ release from the internal store into the cytoplasm occurs via inositol trisphosphate (IP 3 R) and ryanodine receptors (RyR). The internal Ca 2+ stores containing IP 3 R and RyR may be arranged as multiple separate compartments with various IP 3 R and RyR arrangements, or there may be a single structure containing both receptors. The existence of multiple stores is proposed to explain several physiological responses which include the progression of Ca 2+ waves, graded Ca 2+ release from the store and various local responses and sensitivities. We suggest that, rather than multiple stores, a single luminally-continuous store exists in which Ca 2+ is in free diffusional equilibrium throughout. Regulation of Ca 2+ release via IP 3 R and RyR by the local Ca 2+ concentration within the stores explains the apparent existence of multiple stores and physiological processes such as graded Ca 2+ release and Ca 2+ waves. Close positioning of IP 3 R on the store with mitochondria or with receptors on the plasma membrane creates 'IP 3 junctions' to generate local responses on the luminally-continuous store.

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“…Although there is some physiological evidence to support that the RyR isoform present in these cells is similar to the a co-localisation in neurosecretory PC12 cells [27] most studies isoform identified in the mink lung epithelium [23] which is also indicate that these two receptors operate separate Ca 2+ stores, reported to be caffeine-insensitive. We have previously reStudies in the rat vascular smooth muscle cell line A7r5 indicate ported that a ryanodine-sensitive, caffeine-insensitive Ca -,+ rethat the two receptors may operate functionally and spatially lease mechanism is present in intact human myometrial smooth distinct Ca 2÷ stores [28]. However, the use of this cell line may muscle cells [15].…”

Section: Effect Of Ryanodine and Caffeine On 45ca2+ Releasementioning

confidence: 99%

Basic properties of a novel ryanodine‐sensitive, caffeine‐insensitive calcium‐induced calcium release mechanism in permeabilised human vascular smooth muscle cells

Lynn

Gillespie

1995

FEBS Letters

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tion varies among smooth muscle tissues [5]. Caffeine has been Abstract The efllux of 45Ca2+ from preloaded intracellular the accepted means with which to identify Ca2+-induced Ca 2+ stores of saponin-permeabilised human uterine artery smooth release (CICR) in many excitable cells, however, both human muscle cultured cells was used to study the mechanisms nnderlyvascular and myometrial smooth muscle cells do not respond ing Ca 2+ release from the sarcoplasmic reticulum (SR). The present paper demonstrates directly a functional Ca 2+ release mechato caffeine with a release of intracellular Ca 2+ [6]. The IP 3 nism that is dependent on an increase in free Ca 2÷ (100 nM-30 receptor can be activated by IP 3 and Ca 2+, and has been shown pM) and is completely inhibited by 20 pM Ruthenium red. The to be inhibited by caffeine in some cells [3]. The IP 3 receptor amount of Ca 2+ released at 30 pM free Ca 2÷ was reduced by is capable of considerable variability in the sensitivity of IP 3-approximately 50% compared to the release at 10 ~M. This induced Ca 2+ release, which may give rise to the phenomenon Ca2+-induced Ca 2+ release (CICR) mechanism was not sensitive of quantal Ca 2+ release [7]. These variations may depend on to caffeine. Exposure of cells to low free Ca2+-containing solureceptor types differently expressed from different gene prodtions (10 nM) indicated that a component of the CICR mechaucts, alternative splicing or from co-expression of different IP 3 nism may be functional at basal free Ca 2+ levels of 100 nM.receptor subtypes in a single cell [8,9]. The inhibitory action of Application of ryanodine (0.1-100 /tM) induced 45Ca2+ efflux caffeine has also been explained by the reduction of IP 3 producfrom the sarcoplasmic retlculum and this release was also inhibited by 20 ~M Ruthenium red.tion in a dose-dependent manner [10]. Parker and Ivorra using Xenopus oocytes found that caffeine inhibited responses to IP3 Key words." CICR; Ryanodine; Saponin; Smooth muscle; and this may be explained by an antagonistic effect of binding Human vascular of IP 3 to its receptor [11]. The RyR has been studied predominantly in cardiac and skeletal muscle and is sensitive to Ca 2+, Mg 2+ and ATP and may be modulated by calmodulin and activated by caffeine [12]. The 1. Introduction physiological role of the RyR in smooth muscle is uncertain, however CICR, which is presumed to be the mechanism of The processes underlying smooth muscle contraction can RyR-induced Ca 2+ release in cardiac tissue [13], has been suginvolve the activation of voltage and receptor operated Ca 2+ gested to occur in skinned smooth muscle [14]. Microspecinflux pathways and the mobilisation of Ca 2÷ from an intraceltrofluorimetry studies using intact myometrial smooth muscle lular Ca 2÷ store, the sarcoplasmic reticulum (SR). In human cells indicate that a ryanodine-sensitive but caffeine-insensitive uterine artery vascular smooth muscle cells agonists such as Ca 2+ release mechanism may be operational [15]. Therefore, to histamine can activate repetit...

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Functionally and spatially distinct Ca2+ stores are revealed in cultured vascular smooth muscle cells.

Cited by 93 publications

References 47 publications

A Single Luminally Continuous Sarcoplasmic Reticulum with Apparently Separate Ca2+ Stores in Smooth Muscle

A Single Luminally Continuous Sarcoplasmic Reticulum with Apparently Separate Ca2+ Stores in Smooth Muscle

Calcium Mobilization via Intracellular Ion Channels, Store Organization and Mitochondria in Smooth Muscle

Basic properties of a novel ryanodine‐sensitive, caffeine‐insensitive calcium‐induced calcium release mechanism in permeabilised human vascular smooth muscle cells

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