A quantitative model for linking <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.gif" overflow="scroll"><mml:msup><mml:mrow><mml:mtext>Na</mml:mtext></mml:mrow><mml:mrow><mml:mo>+</mml:mo></mml:mrow></mml:msup><mml:mo>/</mml:mo><mml:msup><mml:mrow><mml:mtext>Ca</mml:mtext></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:math> exchanger to SERCA during refilling of the sarcoplasmic reticulum to sustain <mml:math xmlns:mml="http://www.w3.org/1998/Math/

Fameli, Nicola; Breemen, Cornelis van; Kuo, Kuo‐Hsing

doi:10.1016/j.ceca.2007.02.001

Cited by 45 publications

(62 citation statements)

References 37 publications

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“…46 Given the spatial resolution in our experiments (Ϸ480 nm/pixel), the size of the [Na ϩ ] sub-PM transients was comparable to the mean diameter of PM-SR junctions in VSM cells (Ϸ400 nm). 4,39,47 This spatial characteristic of the localized [Na ϩ ] sub-PM transients is consistent with their generation at and spillage from the edges of PM-SR junctions. We recently reported that disruption of PM-SR junctions with calyculin A increased ATP-mediated [Na ϩ ] i elevations and inhibited [Ca 2ϩ ] i elevations, indicating the role of junctions in permitting NCX-mediated Ca 2ϩ entry.…”

Section: Local [Na ؉ ] I Transients and Pm-sr Junctionssupporting

confidence: 48%

“…4,11,39,40 The high density and close apposition of transporters and enzymes in these junctions mediate "linked ion transport," permitting purpose-specific, localized interactions of ion transporters without significant ionic diffusion into the bulk cytosol. 4 Blaustein and colleagues proposed that activation of NSCCs in such junctions could generate the [Na ϩ ] required to mediate NCX- mediated Ca 2ϩ entry.…”

Section: Local [Na ؉ ] I Transients and Pm-sr Junctionsmentioning

confidence: 99%

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Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na ⁺ ] Transients Drive Na ⁺ /Ca ²⁺ Exchanger–Mediated Ca ²⁺ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Poburko

Liao

Lemos

et al. 2007

Circulation Research

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130

108

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Section: Local [Na ؉ ] I Transients and Pm-sr Junctionssupporting

confidence: 48%

Section: Local [Na ؉ ] I Transients and Pm-sr Junctionsmentioning

confidence: 99%

Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na ⁺ ] Transients Drive Na ⁺ /Ca ²⁺ Exchanger–Mediated Ca ²⁺ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Poburko

Liao

Lemos

et al. 2007

Circulation Research

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130

108

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“…The close proximity of the smooth endoplasmic reticulum to the plasma membrane 24 could serve as the structural basis for a putative S1P transport-degradation mechanism. The proteins that transport S1P across the plasma membrane are largely unknown.…”

Section: Indeed Spp1mentioning

confidence: 99%

Role of Sphingosine-1-Phosphate Phosphohydrolase 1 in the Regulation of Resistance Artery Tone

Peter

Lidington²,

Harada³

et al. 2008

Circulation Research

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Abstract-Sphingosine-1-phosphate (S1P), which mediates pleiotropic actions within the vascular system, is a prominent regulator of microvascular tone. By virtue of its S1P-degrading function, we hypothesized that S1P-phosphohydrolase 1 (SPP1) is an important regulator of tone in resistance arteries. Hamster gracilis muscle resistance arteries express mRNA encoding SPP1. Overexpression of SPP1 (via transfection of a SPP1 wt ) reduced resting tone, Ca 2ϩ sensitivity, and myogenic vasoconstriction, whereas reduced SPP1 expression (antisense oligonucleotides) yielded the opposite effects. Expression of a phosphatase-dead mutant of SPP1 (SPP1 H208A ) had no effect on any parameter tested, suggesting that catalytic activity of SPP1 is critical. The enhanced myogenic tone that follows overexpression of S1P-generating enzyme sphingosine kinase 1 (Sk1 wt ) was functionally antagonized by coexpression with SPP1 wt but not SPP1 H208A . SPP1 modulated vasoconstriction in response to 1 to 100 nmol/L exogenous S1P, a concentration range that was characterized as S1P 2 -dependent, based on the effect of S1P 2 inhibition by antisense oligonucleotides and 1 mol/L JTE013. Inhibition of the cystic fibrosis transmembrane regulator (CFTR) (1) restored S1P responses that were attenuated by SPP1 wt overexpression; (2) enhanced myogenic vasoconstriction; but (3) had no effect on noradrenaline responses. We conclude that SPP1 is an endogenous regulator of resistance artery tone that functionally antagonizes the vascular effects of both Sk1 wt and S1P 2 receptor activation. SPP1 accesses extracellular S1P pools in a manner dependent on a functional CFTR transport protein. Our study assigns important roles to both SPP1 and CFTR in the physiological regulation of vascular tone, which influences both tissue perfusion and systemic blood pressure. Key Words: Ca 2ϩ sensitization Ⅲ signal transduction Ⅲ transfection Ⅲ vascular smooth muscle Ⅲ myogenic response Ⅲ cystic fibrosis transmembrane regulator T he bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) is a potent regulator of diverse biological processes, acting both as an intracellular second messenger and as an extracellular receptor ligand. Intracellular S1P (ie, second messenger) has been shown to mediate mitogenic/antiapoptotic 1 and Ca 2ϩ -mobilizing responses, 2 although the mechanisms controlling the latter remain undefined. As an extracellular receptor ligand, S1P can activate small GTPases (eg, RhoA and Rac), phospholipase C and adenylate cyclase via five distinct, G protein-coupled S1P receptors (S1P 1-5 ) (formerly known as EDG family receptors 3 ). Growing evidence supports an important role for S1P in the development and homeostasis of the vascular system, 4 -6 in the pathogenesis of vascular diseases, 7 and in the regulation of acute vascular responses. 8 Our laboratory has recently identified the S1P-generating enzyme sphingosine kinase 1 (Sk1) as a vascular smooth muscle cell (SMC) signaling component necessary for myogenic vasoconstriction in resistance arter...

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“…Furthermore, we found that 8-Br-cAMP repeatedly induced an intracellular Ca 2+ increase after immediate exposure to the cells, ie, the oscillation of Ca 2+ . This 8-Br-cAMP- [33,34] . Interestingly, the behaviors of intracellular Ca 2+ activated by PKA were different from those by PKC activation.…”

Section: Discussionmentioning

confidence: 99%

Functional comparison of the reverse mode of Na+/Ca2+ exchangers NCX1.1 and NCX1.5 expressed in CHO cells

et al. 2013

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concentrations. In contrast, the wild type CHO cells showed a steady increase of [Ca 2+ ] i at higher external Ca 2+ concentrations. The PKC activator PMA (0.3-10 μmol/L) and PKA activator 8-Br-cAMP (10-100 μmol/L) significantly enhanced the reverse mode activity of NCX1.1 and NCX1.5 in CHO cells. NCX1.1 was 2.4-fold more sensitive to PKC activation than NCX1.5, whereas the sensitivity of the two NCX isoforms to PKA activation had no difference. Both PKC-and PKA-enhanced NCX reverse mode activities in CHO cells were suppressed by NCX inhibitor KB-R7943 (30 μmol/L). Conclusion: Both NCX1.1 and NCX1.5 are functional in regulating and maintaining stable [Ca 2+ ] i in CHO cells and differentially regulated by PKA and PKC. The two NCX isoforms might be useful drug targets for heart and brain protection.

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A quantitative model for linking Na+/Ca2+ exchanger to SERCA during refilling of the sarcoplasmic reticulum to sustain
Nicola Fameli
¹
,
Cornelis van Breemen
²
,
Kuo‐Hsing Kuo
³

Cited by 45 publications

References 37 publications

Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na ⁺ ] Transients Drive Na ⁺ /Ca ²⁺ Exchanger–Mediated Ca ²⁺ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na ⁺ ] Transients Drive Na ⁺ /Ca ²⁺ Exchanger–Mediated Ca ²⁺ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Role of Sphingosine-1-Phosphate Phosphohydrolase 1 in the Regulation of Resistance Artery Tone

Functional comparison of the reverse mode of Na+/Ca2+ exchangers NCX1.1 and NCX1.5 expressed in CHO cells

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A quantitative model for linking Na+/Ca2+ exchanger to SERCA during refilling of the sarcoplasmic reticulum to sustain Nicola Fameli1, Cornelis van Breemen2, Kuo‐Hsing Kuo3

Cited by 45 publications

References 37 publications

Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na + ] Transients Drive Na + /Ca 2+ Exchanger–Mediated Ca 2+ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na + ] Transients Drive Na + /Ca 2+ Exchanger–Mediated Ca 2+ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Role of Sphingosine-1-Phosphate Phosphohydrolase 1 in the Regulation of Resistance Artery Tone

Functional comparison of the reverse mode of Na+/Ca2+ exchangers NCX1.1 and NCX1.5 expressed in CHO cells

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Product

Resources

About

A quantitative model for linking Na+/Ca2+ exchanger to SERCA during refilling of the sarcoplasmic reticulum to sustain
Nicola Fameli
¹
,
Cornelis van Breemen
²
,
Kuo‐Hsing Kuo
³

Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na ⁺ ] Transients Drive Na ⁺ /Ca ²⁺ Exchanger–Mediated Ca ²⁺ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells

Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na ⁺ ] Transients Drive Na ⁺ /Ca ²⁺ Exchanger–Mediated Ca ²⁺ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells