Movement of sodium into human platelets induced by ADP

Feinberg, Harold; Sandler, W.C.; Scorer, M.; Breton, Guy C. Le; Grossman, Betty A.; Born, G. V. R.

doi:10.1016/0005-2736(77)90109-2

Cited by 78 publications

(29 citation statements)

References 17 publications

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“…Because collagen-induced increases in [Ca 2ϩ ] i occur when external Na ϩ is maintained at 140 mM, it can then be reasoned that NCX reversal is achieved through a collagen-induced increase in [Na ϩ ] i . Agonist-induced Na ϩ influx has been observed in response to the platelet activators thrombin and ADP (29,30) and collagen (as shown here). In the case of thrombin and ADP, part of the Na ϩ influx has been attributed to activation of the NHE; however, inhibiting the NHE has no effect on the collagen-induced increase in [Ca 2ϩ ] i or aggregation, suggesting another mechanism for the collagen-induced increase in [Na ϩ ] i .…”

Section: Collagen-induced Platelet Aggregation a Ca 2ϩ -Dependentsupporting

confidence: 72%

Mechanism of Collagen Activation in Human Platelets

Roberts

McNicol

Bose

2004

Journal of Biological Chemistry

126

110

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The mechanism of collagen-induced human platelet activation was examined using Ca 2؉ , Na ؉ , and the pHsensitive fluorescent dyes calcium green/fura red, sodium-binding benzofuran isophthalate, and 2 ,7 -bis(2-car- Collagen is the most thrombogenic component of the subendothelium (1). Following vascular damage, collagen is exposed to circulating platelets and both acts as a substrate for the adhesion of platelets (2-4) and induces platelet activation (4). The prevailing evidence proposes that two receptors are involved in the platelet response to collagen; integrin ␣ 2 ␤ 1 acts to adhere platelets to collagen, allowing platelets to interact with the lower affinity receptor glycoprotein VI, which is mainly responsible for platelet activation (3,5).Many of the platelet responses to collagen progress simultaneously when platelets adhere to collagen. At high concentrations, collagen activation of platelets has been shown to proceed through activation of phospholipase C␥2 and subsequent cleavage of phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and 1,2-diacylglycerol (6, 7). Inositol 1,4,5-trisphosphate induces the release of calcium from the dense tubular system (8, 9), whereas 1,2-diacylglycerol activates protein kinase C (10). The collagen-induced inositol 1,4,5-trisphosphate-mediated increase in [Ca 2ϩ ] i is accompanied by an influx of calcium from the extracellular milieu (11, 12). 1,2-Diacylglycerol and calcium mediate the characteristic platelet activation responses such as shape change, granule secretion, and aggregation.At lower concentrations, many of the effects of collagen are enhanced by its production of thromboxane A 2 (TXA) 1 (6, 13-15). The collagen-induced increase in [Ca 2ϩ ] i can be decreased by inhibiting the production of TXA via the pretreatment of platelets with cyclooxygenase inhibitors such as aspirin (11,16,17).Calcium is an important second messenger in the platelet activation cascade. At rest, a [Ca 2ϩ ] i of ϳ100 nM is maintained by a balance between the leak of Ca 2ϩ into the platelet and the concurrent efflux of free Ca 2ϩ across the plasma membrane of the platelet and accumulation in intracellular stores (18,19). Ca 2ϩ is moved out across the plasma membrane through the actions of the plasma membrane Ca 2ϩ -ATPase and the Na ϩ / Ca 2ϩ exchanger (NCX). Plasma membrane Ca 2ϩ -ATPases are membrane-inserted enzymes that use the energy of ATP hydrolysis to move Ca 2ϩ against its gradient and across the membrane. The NCX is capable of moving Ca 2ϩ into or out of the platelet cytosol in exchange for Na ϩ (20, 21). In the resting state, the NCX removes Ca 2ϩ from the platelet cytosol. Internally, Ca 2ϩ is transported into the dense tubular system by the sarco/endoplasmic reticulum Ca 2ϩ -ATPases 2b and 3 (22,23).In response to a moderate dose of collagen (10 g/ml), ϳ70% of the increase in [Ca 2ϩ ] i is due to the influx of Ca 2ϩ from the extracellular milieu, with the remainder as a function of Ca 2ϩ release from the dense tubular system (12). Because voltagega...

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Section: Collagen-induced Platelet Aggregation a Ca 2ϩ -Dependentsupporting

confidence: 72%

Mechanism of Collagen Activation in Human Platelets

Roberts

McNicol

Bose

2004

Journal of Biological Chemistry

126

110

View full text Add to dashboard Cite

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“…The pH change may stimulate spreading by causing actin polymerization. The ionic changes deduced are also consistent with the sodium uptake, pH increase and membrane depolarization that occur in ADP-treated platelets (7,8).…”

supporting

confidence: 77%

“…Feinberg et al (7) have shown that ADP causes an increased influx of sodium into platelets, although the correlation of shape change with sodium influx was not studied. Simons et al (8), using membrane potential and pH sensitive dyes, have shown that the intracellular pH increases -0.3 pH unit in thrombin-stimulated platelets and that the membrane potential depolarizes from a resting level of-50 to -15 mV after stimulation of platelets with ADP or thrombin.…”

mentioning

confidence: 99%

Role of sodium in ADP- and thrombin-induced megakaryocyte spreading.

Leven¹,

Mullikin²,

Nachmias³

1983

The Journal of Cell Biology

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ABSTRACr We investigated the role of sodium in megakaryocyte spreading induced by thrombin and ADP. We found that if extracellular sodium was replaced by lithium, potassium, or choline, spreading was inhibited. When extracellular sodium was present, amiloride or tetrodotoxin inhibited spreading. Using intracellular recording we found spreading to be associated with a permanent membrane depolarization. The extent and rate of thrombin-induced depolarization was reduced when lithium replaced sodium. Unspread cells had an average membrane potential of -44.8 mV. Spread cells had an average membrane potential of -18.46 mV. When choline replaced sodium, or when in the presence of tetrodotoxin and amiloride, the spread cells repolarized, indicating that the depolarization is due to an increase in sodium permeability. Similar treatments did not change the membrane potential of unspread cells. Incubation of megakaryocytes with A23187 together with monensin or methylamine induced spreading. Methylamine occasionally caused spreading by itself, but neither ionophore alone caused spreading. These results indicate that megakaryocyte spreading induced by ADP and thrombin depends on an increase in sodium conductance.Platelets and megakaryocytes, the platelets' precursor cells, have a number of physiological characteristics in common. Both are activated by the platelet agonists ADP, thrombin, and arachidonic acid, and the activation of these ceils is inhibited by prostaglandin E1 (PGE1), tetracaine, and dibutyryl cAMP (1-5). The first step in platelet activation is a change in cell shape: f'dopodia and membrane protrusions form. Isolated, cultured megakaryocytes also respond to platelet agonists by a change in cell shape; fdopodia and a ruffled membrane form and the cells, resting on a surface, become adherent and spread out over the substratum much as platelets spread on glass (4). In both cases, the shape change involves the formation of microfdament nets and bundles from an amorphous precursor material (6; R. M. Leven and V. T. Nachmias, manuscript submitted for publication). The mechanism by which various agents, acting at the cell surface, cause the state of the cytoplasm to change in this way is unknown. However, the close similarities in the responses of these two cell types, and the fact that platelets are themselves fragments of the megakaryocyte cytoplasm, suggest strongly that the mechanism of activation of both platelets and megakaryocytes is very similar, if not the same.Experiments with platelets have recently suggested a possible role for sodium and pH changes as stimuli for the cytoskeletal reorganization that underlies shape change. Feinberg et al. (7) have shown that ADP causes an increased influx of sodium into platelets, although the correlation of shape change with sodium influx was not studied. Simons et al. (8), using membrane potential and pH sensitive dyes, have shown that the intracellular pH increases -0.3 pH unit in thrombin-stimulated platelets and that the membrane potential depolarizes from a restin...

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“…Because the intracellular sodium ion concentration in intact human platelets appears to average 40 mm (Feinstein et al 1977;Feinberg, Sandler, Scorer, LeBreton, Grossman & Born, 1977), exposing the cells to a medium in which the sodium concentration is 10 mm or less should effectively reverse or abolish any intracellular/extracellular sodium gradient, depending on the direction of net sodium movement across the cell membrane. As described previously, platelet vesicular and non-releasable compartments were loaded with 5HT by incubation of cells first with 10-5 M-[14C]5HT (30 min at 37°C) and subsequently with 10-5 M-[3H]5HT (30 min at 37°C).…”

Section: Resultsmentioning

confidence: 99%

Applicability of models for carrier‐mediated serotonin transport to pools of serotonin in intact human platelets.

Costa¹,

Murphy²,

Stark³

1981

The Journal of Physiology

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SUMMARYIntact human platelets can accumulate serotonin (5HT) in compartments which are vesicular (thrombin-releasable) or extra-vesicular (non-thrombin-releasable).1. The net accumulation of extracellular 5HT in either compartment is not coupled in a reciprocal fashion to the presence of appropriate sodium gradients across the cell plasma membrane, and 5HT already present in either compartment is not removed when trans-membrane sodium gradients are abolished or reversed.2. Net counter-transport of 5HT in either compartment is not detectable. 3. The data are not consistent with transport models such as that for glucose in which appropriate sodium gradients produce gradients of a co-transported molecule, or with models in which counter-transport can occur.

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Movement of sodium into human platelets induced by ADP

Cited by 78 publications

References 17 publications

Mechanism of Collagen Activation in Human Platelets

Mechanism of Collagen Activation in Human Platelets

Role of sodium in ADP- and thrombin-induced megakaryocyte spreading.

Applicability of models for carrier‐mediated serotonin transport to pools of serotonin in intact human platelets.

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