Increased intracellular Na+ augments mobilization of Ca2+ from SR in vascular smooth muscle cells

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

doi:10.1152/ajpcell.1994.266.1.c311

Cited by 49 publications

(24 citation statements)

References 18 publications

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“…In the relatively ouabainresistant A7r5 cells, 1 M ouabain induces proliferation comparable to that obtained with 1 nM ouabain in CSVSMCs (1,3). It is most important to note that it has been clearly shown that this concentration of ouabain has no effect on the Na pump of A7r5 cells or rat vessels, so there would be no significant alteration of cytoplasmic ion content (8,9). The results of the experiments shown in Fig.…”

Section: Colocalization Of Nasupporting

confidence: 54%

Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype

Liu

Abramowitz²,

Askari³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype. Am J Physiol Heart Circ Physiol 287: H2173-H2182, 2004. First published July 15, 2004 doi:10.1152/ajpheart.00352.2004.-We have shown earlier that low concentrations of ouabain that do not perturb the ionic milieu can initiate proliferation of vascular smooth muscle cells (VSMCs) in the synthetic phenotype from three different species: canine, rodent, and human. This effect occurs by activation of Src and the epidermal growth factor receptor (EGFR), and thus supports the concept of an additional, nonionic, transducing function of the Na pump. The present study presents data suggesting that such activation occurs through specific Na pump sites localized to the caveolae, and subsequent interactions with selected signaling proteins resident within the same membrane microdomain. Our data show that at rest, 30% of the total number of Na pumps are concentrated within the caveolae. When the various VSMCs were treated with proliferating concentrations of ouabain, the key protein content in isolated caveolae was increased. However, the recruited proteins were different between the different tissues. Thus ouabain activated the recruitment of both the Na pump ␣ 1-subunit and EGFR in the caveolae from rat A7r5 cells, whereas in both human and canine cells, ouabain activated the recruitment of Src, with the caveolar content of the other proteins remaining constant. These data demonstrate that ouabain interacts with the ␣1-subunit of the Na pump that resides within the caveolar domain, and such interaction selectively recruits signal transducing proteins to this microdomain resulting in their activation, which is necessary for the initiation of the proliferative cascade. Na pump; ouabain signaling; vascular smooth muscle proliferation THE NA PUMP maintains normal ion gradients across the cell membrane of virtually all mammalian cells, and the mechanism of ion transport has been studied extensively for many years (7,21). Recently, however, it has become apparent that pump function can be modulated by a variety of interacting proteins with mechanisms other than enzymatic phosphorylation of PKA and PKC. Such protein modulators are the FXYD family of proteins, i.e., phospholemman (15, 16), the ␥-subunit (28), and corticosteroid hormone-induced factor (16), which have been known for some time but whose functions have only recently been delineated. Their interaction with the Na pump can alter affinity for both ATP and ions (42).However, these are not the only protein moieties that can interact with the pump. Recently, a number of studies have appeared indicating that the pump can also interact with proteins generally associated with the well-known growth-related transducing cascades. The functional manifestation of these pump-protein interactions are quite tissue specific (see below), and a common bond between all of these observations is that they are initiated by the binding of the cardiac glycoside inhibitor oua...

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Section: Colocalization Of Nasupporting

confidence: 54%

Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype

Liu

Abramowitz²,

Askari³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…After [Na ϩ ] o was reduced to 100 mmol/L the cell pairs uncoupled already at ϩ10 mV ( Figure 5A and B). The rate of the capacitance decay was voltage-dependent ] i is buffered at a low concentration (9). The experimental results corresponding to these interventions are presented in Table. ( Figure 5A): the more positive the holding potential, the more rapidly cells uncoupled ( Figure 5C).…”

Section: Resultsmentioning

confidence: 99%

Interaction Between Na ⁺ /K ⁺ -Pump and Na ⁺ /Ca ²⁺ -Exchanger Modulates Intercellular Communication

Matchkov

Gustafsson

Rahman

et al. 2007

Circulation Research

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Abstract-Ouabain, a specific inhibitor of the Na ϩ /K ϩ -pump, has previously been shown to interfere with intercellular communication. Here we test the hypothesis that the communication between vascular smooth muscle cells is regulated through an interaction between the Na ϩ /K ϩ -pump and the Na ϩ /Ca 2ϩ -exchanger leading to an increase in the intracellular calcium concentration ([Ca 2ϩ ] i ) in discrete areas near the plasma membrane. [Ca 2ϩ ] i in smooth muscle cells was imaged in cultured rat aortic smooth muscle cell pairs (A7r5) and in rat mesenteric small artery segments simultaneously with force. In A7r5 coupling between cells was estimated by measuring membrane capacitance. Smooth muscle cells were uncoupled when the Na

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“…When Ca2 +-entry is prevented under Ca21-free conditions or with diltiazem, the high K+-induced Ca2+ response is due to the remaining direct molecular interaction between the Ca2`channel and the ryanodine receptor (Schneider & Chandler, 1973;Meissner, 1994) (Grassi et al, 1993 tying of the internal store (Grassi et al, 1993). Recently, increased cytosolic Na' has been shown to augment thapsigargin-induced Ca2" release in smooth muscle cells (Borin et al, 1994). Whether a similar mechanism is involved in the nAChR-mediated mobilization of Ca2" from internal stores remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Different mechanisms of Ca²⁺‐handling following nicotinic acetylcholine receptor stimulation, P_2U‐purinoceptor stimulation and K⁺‐induced depolarization in C2C12 myotubes

Henning

Duin

Popta

et al. 1996

British J Pharmacology

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1 The increase in intracellular Ca2+ on nicotinic acetylcholine receptor (nAChR) stimulation, P2U-purinoceptor stimulation and K+-induced depolarization was investigated in mouse C2C12 myotubes by use of fura-2 fluorescence to characterize the intracellular organisation of Ca2+ releasing stores and Ca2+ -entry process.2 Stimulation of nAChRs with carbachol induced a rapid rise in internal Ca2+ (EC50 = 0.85 + 0.09 gM), followed by a sustained phase. The Ca2+ response evoked by carbachol (10 gM) was completely blocked by the nAChR antagonist, pancuronium (3 gM), but was not affected by the muscarinic antagonist, atropine (3 gM), or under conditions when Ca2+ entry was blocked by La3`(50 gM) or diltiazem (10 gM). Addition of pancuronium (3 gM) during the sustained phase of the carbachol-evoked response did not affect this phase.3 Stimulation of P2U purinoceptors with ATP (1 mM) induced a somewhat higher biphasic Ca2+ response (EC50 of the rapid phase: 8.72+0.08 gM) than with carbachol. Pretreatment with La3+ abolished the sustained phase of the ATP-induced Ca2+ response, while the response was unaffected by diltiazem or pancuronium. 4 Stimulation of the cells with high K+ (60 mM), producing the same depolarization as with carbachol (10 gM), induced a rapid monophasic Ca2`response, insensitive to diltiazem, pancuronium or La3 .5 Under Ca2+ -free conditions, the sustained phase of the carbachol-and ATP-evoked responses were abolished. Pre-emptying of depolarization-sensitive stores by high K+ under Ca2+-free conditions did not affect the carbachol-or ATP-evoked Ca2+ mobilization and vice versa. Preincubation of the cells with ATP in the absence of extracellular Ca2+ decreased the amplitude of the subsequent carbacholinduced Ca2+ response to 11 %, while in the reverse procedure the ATP-induced response was decreased to 65%. Ca2+ mobilization evoked by simultaneous addition of optimal concentrations of carbachol and ATP was increased compared to levels obtained with either agonist. 6 Preincubation with high K+ under normal conditions abolished the sustained phase of the ATPevoked Ca2+ response. The carbachol response consisted only of the sustained phase in the presence of high K+.7 The carbachol-induced Ca2+ response was completely abolished under low Na+/Ca2+ -free conditions, while under low Na+ conditions only a sustained Ca2+ response was observed. The ATPand K+-induced responses were changed compared to Ca2+-free conditions. 8 ATP (300 gM) induced the formation of Ins(1,4,5)P3 under Ca2+-free conditions with a comparable time course to that found for the rise in internal Ca2 . In contrast to ATP, carbachol (10 gM) did not affect Ins(1,4,5)P3 levels under Ca2+-free conditions. 9 It is concluded that the Ca2+ release from discrete stores of C2C12 myotubes is induced by stimulation of nAChRs, P2U-purinoceptors and by high K+. Only the P2U-purinoceptor and nAChR activated stores show considerable overlap in releasable Ca2. Sustained Ca2+-entry is activated by stimulation of nAChRs and P2u-purinoceptors via separate i...

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Increased intracellular Na+ augments mobilization of Ca2+ from SR in vascular smooth muscle cells

Cited by 49 publications

References 18 publications

Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype

Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype

Interaction Between Na ⁺ /K ⁺ -Pump and Na ⁺ /Ca ²⁺ -Exchanger Modulates Intercellular Communication

Different mechanisms of Ca²⁺‐handling following nicotinic acetylcholine receptor stimulation, P_2U‐purinoceptor stimulation and K⁺‐induced depolarization in C2C12 myotubes

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Increased intracellular Na+ augments mobilization of Ca2+ from SR in vascular smooth muscle cells

Cited by 49 publications

References 18 publications

Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype

Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype

Interaction Between Na + /K + -Pump and Na + /Ca 2+ -Exchanger Modulates Intercellular Communication

Different mechanisms of Ca2+‐handling following nicotinic acetylcholine receptor stimulation, P2U‐purinoceptor stimulation and K+‐induced depolarization in C2C12 myotubes

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Product

Resources

About

Interaction Between Na ⁺ /K ⁺ -Pump and Na ⁺ /Ca ²⁺ -Exchanger Modulates Intercellular Communication

Different mechanisms of Ca²⁺‐handling following nicotinic acetylcholine receptor stimulation, P_2U‐purinoceptor stimulation and K⁺‐induced depolarization in C2C12 myotubes