共查询到20条相似文献,搜索用时 15 毫秒
1.
Adrian M. Duke Philip M. Hopkins Sarah C. Calaghan Jane P. Halsall Derek S. Steele 《The Journal of biological chemistry》2010,285(33):25645-25653
In malignant hyperthermia (MH), mutations in RyR1 underlie direct activation of the channel by volatile anesthetics, leading to muscle contracture and a life-threatening increase in core body temperature. The aim of the present study was to establish whether the associated depletion of sarcoplasmic reticulum (SR) Ca2+ triggers sarcolemmal Ca2+ influx via store-operated Ca2+ entry (SOCE). Samples of vastus medialis muscle were obtained from patients undergoing assessment for MH susceptibility using the in vitro contracture test. Single fibers were mechanically skinned, and confocal microscopy was used to detect changes in [Ca2+] either within the resealed t-system ([Ca2+]t-sys) or within the cytosol. In normal fibers, halothane (0.5 mm) failed to initiate SR Ca2+ release or Ca2+t-sys depletion. However, in MH-susceptible (MHS) fibers, halothane induced both SR Ca2+ release and Ca2+t-sys depletion, consistent with SOCE. In some MHS fibers, halothane-induced SR Ca2+ release took the form of a propagated wave, which was temporally coupled to a wave of Ca2+t-sys depletion. SOCE was potently inhibited by “extracellular” application of a STIM1 antibody trapped within the t-system but not when the antibody was denatured by heating. In conclusion, (i) in human MHS muscle, SR Ca2+ depletion induced by a level of volatile anesthetic within the clinical range is sufficient to induce SOCE, which is tightly coupled to SR Ca2+ release; (ii) sarcolemmal STIM1 has an important role in regulating SOCE; and (iii) sustained SOCE from an effectively infinite extracellular Ca2+ pool may contribute to the maintained rise in cytosolic [Ca2+] that underlies MH. 相似文献
2.
3.
Xiaoli Zhao Choon Kee Min Jae-Kyun Ko Do Han Kim Jianjie Ma 《Biophysical journal》2010,99(5):1556-1564
Store-operated Ca2+ entry (SOCE) contributes to Ca2+ handling in normal skeletal muscle function, as well as the progression of muscular dystrophy and sarcopenia, yet the mechanisms underlying the change in SOCE in these states remain unclear. Previously we showed that calsequestrin-1 (CSQ1) participated in retrograde regulation of SOCE in cultured skeletal myotubes. In this study, we used small-hairpin RNA to determine whether knockdown of CSQ1 in adult mouse skeletal muscle can influence SOCE activity and muscle function. Small-hairpin RNA against CSQ1 was introduced into flexor digitorum brevis muscles using electroporation. Transfected fibers were isolated for SOCE measurements using the Mn2+ fluorescence-quenching method. At room temperature, the SOCE induced by submaximal depletion of the SR Ca2+ store was significantly enhanced in CSQ1-knockdown muscle fibers. When temperature of the bathing solution was increased to 39°C, CSQ1-knockdown muscle fibers displayed a significant increase in Ca2+ permeability across the surface membrane likely via the SOCE pathway, and a corresponding elevation in cytosolic Ca2+ as compared to control fibers. Preincubation with azumolene, an analog of dantrolene used for the treatment of malignant hyperthermia (MH), suppressed the elevated SOCE in CSQ1-knockdown fibers. Because the CSQ1-knockout mice develop similar MH phenotypes, this inhibitory effect of azumolene on SOCE suggests that elevated extracellular Ca2+ entry in skeletal muscle may be a key factor for the pathophysiological changes in intracellular Ca2+ signaling in MH. 相似文献
4.
An unconventional interaction between SPCA2, an isoform of the Golgi secretory pathway Ca2+-ATPase, and the Ca2+ influx channel Orai1, has previously been shown to contribute to elevated Ca2+ influx in breast cancer derived cells. In order to investigate the physiological role of this interaction, we examined expression and localization of SPCA2 and Orai1 in mouse lactating mammary glands. We observed co-induction and co-immunoprecipitation of both proteins, and isoform-specific differences in the localization of SPCA1 and SPCA2. Three-dimensional cultures of normal mouse mammary epithelial cells were established using lactogenic hormones and basement membrane. The mammospheres displayed elevated Ca2+ influx by store independent mechanisms, consistent with upregulation of both SPCA2 and Orai1. Knockdown of either SPCA2 or Orai1 severely depleted Ca2+ influx and interfered with mammosphere differentiation. We show that SPCA2 is required for plasma membrane trafficking of Orai1 in mouse mammary epithelial cells and that this function can be replaced, at least in part, by a membrane-anchored C-terminal domain of SPCA2. These findings clearly show that SPCA2 and Orai1 function together to regulate Store-independent Ca2+ entry (SICE), which mediates the massive basolateral Ca2+ influx into mammary epithelia to support the large calcium transport requirements for milk secretion. 相似文献
5.
Zhang SL Kozak JA Jiang W Yeromin AV Chen J Yu Y Penna A Shen W Chi V Cahalan MD 《The Journal of biological chemistry》2008,283(25):17662-17671
We evaluated currents induced by expression of human homologs of Orai together with STIM1 in human embryonic kidney cells. When co-expressed with STIM1, Orai1 induced a large inwardly rectifying Ca(2+)-selective current with Ca(2+)-induced slow inactivation. A point mutation of Orai1 (E106D) altered the ion selectivity of the induced Ca(2+) release-activated Ca(2+) (CRAC)-like current while retaining an inwardly rectifying I-V characteristic. Expression of the C-terminal portion of STIM1 with Orai1 was sufficient to generate CRAC current without store depletion. 2-APB activated a large relatively nonselective current in STIM1 and Orai3 co-expressing cells. 2-APB also induced Ca(2+) influx in Orai3-expressing cells without store depletion or co-expression of STIM1. The Orai3 current induced by 2-APB exhibited outward rectification and an inward component representing a mixed calcium and monovalent current. A pore mutant of Orai3 inhibited store-operated Ca(2+) entry and did not carry significant current in response to either store depletion or addition of 2-APB. Analysis of a series of Orai1-3 chimeras revealed the structural determinant responsible for 2-APB-induced current within the sequence from the second to third transmembrane segment of Orai3. The Orai3 current induced by 2-APB may reflect a store-independent mode of CRAC channel activation that opens a relatively nonselective cation pore. 相似文献
6.
《Cell calcium》2019
Ca2+ channels play an important role in the development of different types of cancer, and considerable progress has been made to understand the pathophysiological mechanisms underlying the role of Ca2+ influx in the development of different cancer hallmarks. Orai1 is among the most ubiquitous and multifunctional Ca2+ channels. Orai1 mediates the highly Ca2+-selective Ca2+ release-activated current (ICRAC) and participates in the less Ca2+-selective store-operated current (ISOC), along with STIM1 or STIM1 and TRPC1, respectively. Furthermore, Orai1 contributes to a variety of store-independent Ca2+ influx mechanisms, including the arachidonate-regulated Ca2+ current, together with Orai3 and the plasma membrane resident pool of STIM1, as well as the constitutive Ca2+ influx processes activated by the secretory pathway Ca2+-ATPase-2 (SPCA2) or supported by physical and functional interaction with the small conductance Ca2+-activated K+ channel 3 (SK3) or the voltage-dependent Kv10.1 channel. This review summarizes the current knowledge concerning the store-independent mechanisms of Ca2+ influx activation through Orai1 channels and their role in the development of different cancer features. 相似文献
7.
A New View of Ca2+ Sparks in Frog Skeletal Muscle 总被引:2,自引:0,他引:2
Withrow Gil Wier 《The Journal of general physiology》2001,118(6):649-652
8.
Mapping the interacting domains of STIM1 and Orai1 in Ca2+ release-activated Ca2+ channel activation 总被引:1,自引:0,他引:1
STIM1 and Orai1 are essential components of Ca(2+) release-activated Ca(2+) channels (CRACs). After endoplasmic reticulum Ca(2+) store depletion, STIM1 in the endoplasmic reticulum aggregates and migrates toward the cell periphery to co-localize with Orai1 on the opposing plasma membrane. Little is known about the roles of different domains of STIM1 and Orai1 in protein clustering, migration, interaction, and, ultimately, opening CRAC channels. Here we demonstrate that the coiled-coil domain in the C terminus of STIM1 is crucial for its aggregation. Amino acids 425-671 of STIM1, which contain a serine-proline-rich region, are important for the correct targeting of the STIM1 cluster to the cell periphery after calcium store depletion. The polycationic region in the C-terminal tail of STIM1 also helps STIM1 targeting but is not essential for CRAC channel activation. The cytoplasmic C terminus but not the N terminus of Orai1 is required for its interaction with STIM1. We further identify a highly conserved region in the N terminus of Orai1 (amino acids 74-90) that is necessary for CRAC channel opening. Finally, we show that the transmembrane domain of Orai1 participates in Orai1-Orai1 interactions. 相似文献
9.
Francisco Altamirano José M. Eltit Ga?lle Robin Nancy Linares Xudong Ding Isaac N. Pessah Paul D. Allen José R. López 《The Journal of biological chemistry》2014,289(27):19180-19190
Malignant hyperthermia (MH) is potentially fatal pharmacogenetic disorder of skeletal muscle caused by intracellular Ca2+ dysregulation. NCX is a bidirectional transporter that effluxes (forward mode) or influxes (reverse mode) Ca2+ depending on cellular activity. Resting intracellular calcium ([Ca2+]r) and sodium ([Na+]r) concentrations are elevated in MH susceptible (MHS) swine and murine muscles compared with their normal (MHN) counterparts, although the contribution of NCX is unclear. Lowering [Na+]e elevates [Ca2+]r in both MHN and MHS swine muscle fibers and it is prevented by removal of extracellular Ca2+ or reduced by t-tubule disruption, in both genotypes. KB-R7943, a nonselective NCX3 blocker, reduced [Ca2+]r in both swine and murine MHN and MHS muscle fibers at rest and decreased the magnitude of the elevation of [Ca2+]r observed in MHS fibers after exposure to halothane. YM-244769, a high affinity reverse mode NCX3 blocker, reduces [Ca2+]r in MHS muscle fibers and decreases the amplitude of [Ca2+]r rise triggered by halothane, but had no effect on [Ca2+]r in MHN muscle. In addition, YM-244769 reduced the peak and area under the curve of the Ca2+ transient elicited by high [K+]e and increased its rate of decay in MHS muscle fibers. siRNA knockdown of NCX3 in MHS myotubes reduced [Ca2+]r and the Ca2+ transient area induced by high [K+]e. These results demonstrate a functional NCX3 in skeletal muscle whose activity is enhanced in MHS. Moreover reverse mode NCX3 contributes to the Ca2+ transients associated with K+-induced depolarization and the halothane-triggered MH episode in MHS muscle fibers. 相似文献
10.
Xiaoli Zhao Daiju Yamazaki Ki Ho Park Shinji Komazaki Andoria Tjondrokoesoemo Miyuki Nishi Peihui Lin Yutaka Hirata Marco Brotto Hiroshi Takeshima Jianjie Ma 《The Journal of biological chemistry》2010,285(48):37370-37376
The sarcoplasmic reticulum (SR) of skeletal muscle contains K+, Cl−, and H+ channels may facilitate charge neutralization during Ca2+ release. Our recent studies have identified trimeric intracellular cation (TRIC) channels on SR as an essential counter-ion permeability pathway associated with rapid Ca2+ release from intracellular stores. Skeletal muscle contains TRIC-A and TRIC-B isoforms as predominant and minor components, respectively. Here we test the physiological function of TRIC-A in skeletal muscle. Biochemical assay revealed abundant expression of TRIC-A relative to the skeletal muscle ryanodine receptor with a molar ratio of TRIC-A/ryanodine receptor ∼5:1. Electron microscopy with the tric-a−/− skeletal muscle showed Ca2+ overload inside the SR with frequent formation of Ca2+ deposits compared with the wild type muscle. This elevated SR Ca2+ pool in the tric-a−/− muscle could be released by caffeine, whereas the elemental Ca2+ release events, e.g. osmotic stress-induced Ca2+ spark activities, were significantly reduced likely reflecting compromised counter-ion movement across the SR. Ex vivo physiological test identified the appearance of “alternan” behavior with isolated tric-a−/− skeletal muscle, i.e. transient and drastic increase in contractile force appeared within the decreasing force profile during repetitive fatigue stimulation. Inhibition of SR/endoplasmic reticulum Ca2+ ATPase function could lead to aggravation of the stress-induced alternans in the tric-a−/− muscle. Our data suggests that absence of TRIC-A may lead to Ca2+ overload in SR, which in combination with the reduced counter-ion movement may lead to instability of Ca2+ movement across the SR membrane. The observed alternan behavior with the tric-a−/− muscle may reflect a skeletal muscle version of store overload-induced Ca2+ release that has been reported in the cardiac muscle under stress conditions. 相似文献
11.
Dynamic changes in cytosolic and nuclear Ca2+ concentration are reported to play a critical regulatory role in different aspects of skeletal muscle development and differentiation. Here we review our current knowledge of the spatial dynamics of Ca2+ signals generated during muscle development in mouse, rat, and Xenopus myocytes in culture, in the exposed myotome of dissected Xenopus embryos, and in intact normally developing zebrafish. It is becoming clear that subcellular domains, either membrane-bound or otherwise, may have their own Ca2+ signaling signatures. Thus, to understand the roles played by myogenic Ca2+ signaling, we must consider: (1) the triggers and targets within these signaling domains; (2) interdomain signaling, and (3) how these Ca2+ signals integrate with other signaling networks involved in myogenesis. Imaging techniques that are currently available to provide direct visualization of these Ca2+ signals are also described.The recognition of Ca2+ as a key regulator of muscle contraction dates back to Sydney Ringer''s seminal observations in the latter part of the 19th Century (Ringer 1883; Ringer 1886; Ringer and Buxton 1887; see reviews by Martonosi 2000; Szent-Györgyi 2004). More recently, evidence is steadily accumulating to support the proposition that Ca2+ also plays a necessary and essential role in regulating embryonic muscle development and differentiation (Flucher and Andrews 1993; Ferrari et al. 1996; Lorenzon et al. 1997; Ferrari and Spitzer 1998, 1999; Wu et al. 2000; Powell et al. 2001; Jaimovich and Carrasco 2002; Li et al. 2004; Brennan et al. 2005; Harris et al. 2005; Campbell et al. 2006; Terry et al. 2006; Fujita et al. 2007; and see reviews by Berchtold et al. 2000; Ferrari et al. 2006; Al-Shanti and Stewart 2009). What is currently lacking, however, is extensive direct visualization of the spatial dynamics of the Ca2+ signals generated by developing and differentiating muscle cells. This is especially so concerning in situ studies. The object of this article, therefore, is to review and report the current state of our understanding concerning the spatial nature of Ca2+ signaling during embryonic muscle development, especially from an in vivo perspective, and to suggest possible directions for future research. The focus of our article is embryonic skeletal muscle development because of this being an area of significant current interest. Several of the basic observations reported, however, may also be common to cardiac muscle development and in some cases to smooth muscle development. What the recent development of reliable imaging techniques has most certainly done, is to add an extra dimension of complexity to understanding the roles played by Ca2+ signaling in skeletal muscle development. For example, it is clear that membrane-bound subcellular compartments, such as the nucleus (Jaimovich and Carrasco 2002), may have endogenous Ca2+ signaling activities, as do specific cytoplasmic domains, such as the subsarcolemmal space (Campbell et al. 2006). How these Ca2+ signals interact with specific down-stream targets within their particular domain, and how they might serve to communicate information among domains, will most certainly be one of the future challenges in elucidating the Ca2+-mediated regulation of muscle development.Any methodology used to study the properties of biological molecules and how they interact during development should ideally provide spatial information, because researchers increasingly need to integrate data about the interactions that underlie a biological process (such as differentiation) with information regarding the precise location within cells or an embryo where these interactions take place. Current Ca2+ imaging techniques are beginning to provide us with this spatial information, and are thus opening up exciting new avenues of investigation in our quest to understand the signaling pathways that regulate muscle development (Animal Intact animals/Cells in culture Ca2+ reporter Reporter Loading Protocol Reference Rat 1° cultures prepared from hind limb muscle of neonatal rat pups Fluo 3-AM Cells incubated in 5.4 µM reporter for 30 min at 25°C. Jaimovich et al. 2000 Mouse Myotubes grown from C2C12 subclone of the C2 mouse muscle cell line Fluo 3-AM Incubated in 5 µM reporter plus 0.1% pluronic F-127 for 1 h at r.t. Flucher and Andrews 1993 Myotubes isolated from the intercostal muscles of E18 wild-type and RyR type 3-null mice. Fluo 3-AM Cells incubated with 4 µM for 30 min at r.t. Conklin et al. 1999b Myotubes in culture prepared from newborn mice. Fluo 3-AM Cells incubated in 10 µM for 20 min. Shirokova et al. 1999 1° cultures prepared from hind limb muscle from newborn mice. Fluo 3-AM Cells incubated in 5.4 µM reporter for 30 min at 25°C. Powell et al. 2001 Embryonic day 18 (E18) isolated diaphragm muscle fibers Fluo 4-AM Incubated in 10 µM reporter for 30 min. Chun et al. 2003 Chick Myotubes prepared from leg or breast of 11-day chick embryos Fluo 3-AM Incubated in 5 µM reporter plus 0.1% pluronic F-127 for 1 h at r.t. Flucher and Andrews 1993 Myoblasts isolated from thigh muscle of E12 embryos. Fluo 3-AM 1 mM stock was diluted 1:200 with 0.2% pluronic F-127. Cells were incubated for 60 min at r.t. in the dark. Tabata et al. 2006 Xenopus Exposed myotome in dissected embryo Fluo-3 AM Incubated dissected tissue in 10 µM reporter for 30–60 min. Ferrari and Spitzer 1999 1° myocyte cultures prepared from stage 15 Xenopus embryos. Fluo-4 AM Cells incubated in 2 µM reporter plus 0.01% pluronic F-127 for 60 min. Campbell et al. 2006 Zebrafish Intact animals Calcium green-1 dextran (10S) Reporter at 20 mM was injected into a single blastomere between the 32- and 128-cell stage. Zimprich et al. 1998 Intact animals Oregon Green 488 BAPTA dextran Single blastomeres from 32-cell stage embryos injected with reporter (i.c. 100 µM) and tetramethylrhodamine dextran (i.c. 40 µM). Ashworth et al. 2001 Intact animals Oregon Green 488 BAPTA dextran Microinjected with rhodamine dextran to give an intracellular concentration of ∼40 µM. Ashworth 2004 Intact animals Aequorin aEmbryos injected with 700 pg aeq-mRNA at the 1-cell stage and then incubated with 50 µM f-coelenterazine from the 64-cell stage. Cheung et al. 2006 Intact animals Aequorin Transgenic fish that express apoaequorin in the skeletal muscles were incubated with 50 µM f-coelenterazine from the 8-cell stage. Cheung et al. 2010