Search PubMed⌕ Search

Biomedical subjects

M A Devynck

Publications and source records attributed to M A Devynck.

At least 37 records · Page 2Linked to original sources
PubMed1997

Elaboration and use of nickel planar macrocyclic complex-based sensors for the direct electrochemical measurement of nitric oxide in biological media.

We describe here the electrochemical detection of nitric oxide, NO, in biological systems by using chemically modified ultramicro carbon electrodes. In the first part of the paper, the different steps involved in the electrochemical preparation and characterization of the nickel-based sensor are described. This is illustrated by the use of nickel(II) tetrasulfonated phthalocyanine complex. The second part of the paper describes two examples of the direct electrochemical measurement of NO production in human blood platelets and endothelial cells from umbilical cord vein.

Biosensing Techniques↗
PubMed1997

Cytosolic pH and calcium in Dahl salt-sensitive and salt-resistant rats: the relationship to plasma lipids.

OBJECTIVE: To search for alterations of cytosolic pH and cell calcium handling in platelets and erythrocytes of Dahl rats susceptible and resistant to salt-induced hypertension. DESIGN AND METHODS: Blood pressure, plasma lipids, platelet cytosolic calcium concentration ([Ca2+]i) and pH (pHi) together with thrombin-induced changes in these parameters as well as erythrocyte [Ca2+]i and 45Ca influx were determined in Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats aged 9, 15 and 24 weeks, which were fed a low-salt diet (0.3% NaCl), and in animals fed high-salt diet (4% NaCl) for 5-10 weeks since weaning. RESULTS: With a low salt intake platelet pHi was lower in SS/Jr than it was in SR/Jr rats, whereas basal platelet [Ca2+]i was similar in rats of both strains. The difference in basal pHi between SS/Jr and SR/Jr rats increased progressively with age of animals. A high salt intake from youth did not influence platelet [Ca2+]i in rats of either strain but it caused an earlier decrease in pHi in SR/Jr than it did in SS/Jr rats. Thrombin stimulation induced similar elevations of pHi and [Ca2+]i in rats of both strains, irrespective of age, salt intake and response of blood pressure to salt intake. Erythrocyte 45Ca influx and [Ca2+]i were greater for SS/Jr rats but only the latter parameter was correlated positively to blood pressure. Both regulation of platelet pHi and erythrocyte Ca2+ handling were significantly related to plasma lipid levels. CONCLUSIONS: Platelets of SS/Jr rats fed a low-salt diet were characterized by a lower basal cytosolic pHi but unchanged [Ca2+]i relative to those of SR/Jr rats. Hypertension induced by high salt intake was associated with increased erythrocyte [Ca2+]i but not with elevation of platelet [Ca2+]i or alteration of response to stimulation with thrombin.

Animals↗
PubMed1997

Inhibition of Ca2+ uptake into A7r5 vascular smooth muscle cells by farnesol: lack of effect on membrane fluidity and Ca2+-ATPase activities.

BACKGROUND: Previous studies have shown that farnesol, a 15-carbon nonsterol derivative of mevalonic acid, inhibits vasoconstriction. Because of its lipophilic properties, we hypothesized that farnesol increased membrane dynamics, thus reducing uptake of Ca2+ and contraction. OBJECTIVE: To characterize the effect of farnesol on cell membrane fluidity. DESIGN: The study was conducted using A7r5 cells, a rat aortic vascular smooth muscle cell line. Inhibition of Ca2+ uptake by farnesol was first established in these cells. Then, the effect of farnesol on membrane dynamics was determined. Finally, to ascertain that activation of Ca2+ extrusion and reuptake processes by farnesol did not occur, Ca2+-ATPase activity was examined. METHODS: Membrane fluidity in cell homogenates was estimated using two fluorescent dyes (1,6-diphenyl-1,3,5-hexatriene) and (1-[-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene). Ca2+ uptake was determined by monitoring the changes in cytosolic Ca2+ concentration ([Ca2+]i) in fura-2-loaded cells after addition of KCI. Ca2+-ATPase activity was measured in 100000 x g cell fractions. RESULTS: Farnesol reduced KCI-induced (Ca2+]i transients significantly (P < 0.001), but did not modify membrane dynamic properties [0.214+/-0.007 versus 0.218+/-0.007 (n = 10) and 0.142+/-0.002 versus 0.146+/-0.003 (n = 5) for 1 -[-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene anisotropies, respectively; NS]. Administration of up to 30 micromol/l farnesol did not affect Ca2+-ATPase activity. CONCLUSION: Farnesol inhibits KCI-dependent rise of [Ca2+]i in A7r5 cells. This effect of farnesol is not related to a global change in plasma membrane lipid organization or to activation of Ca2+ pumps. Other mechanisms such as direct inhibition of voltage-dependent Ca2+ channels could therefore explain the biologic action of farnesol in the vascular tissue.

Animals↗
PubMed1996

Human immunoglobulins inhibit thrombin-induced Ca2+ movements and nitric oxide production in endothelial cells.

Binding of natural antibodies to endothelial cell plays an important role in hyperacute xenograft rejection between discordant species. Human intravenous immunoglobulins (IVIg) delay this hyperacute rejection, but their mechanisms of action on endothelial cells have to be defined. Here we demonstrate that IVIg dose-dependently prevent thrombin from eliciting cytosolic Ca2+ movements and nitric oxide (NO) production in aortic endothelial cells from guinea pig. The Ca2+ response to thrombin was similarly affected by IVIg whether they were removed or not from the incubation medium before stimulation. Pretreatment by rat natural antibodies also suppress the thrombin-induced Ca2+ peak corresponding to Ca2+ release from intracellular stores but stimulate the subsequent sustained increase in [Ca2+]i and the release of NO. The action of human intravenous immunoglobulins seems to be selective for the thrombin receptor because they do not affect [Ca2+]i and NO responses to endothelin-1 or thapsigargin. However, these antibodies also suppress the first phase of the cytosolic Ca2+ response to ATP, which does not release NO under our experimental conditions. These observations raise the possibility that IVIg selectively interact with targets localized on plasma membrane of endothelial cells for controlling receptor-activated Ca2+ pathways and NO release.

Animals↗
PubMed1996

Endothelin-3, Ca2+ mobilization and cyclic GMP content in human platelets.

As previously described for endothelin-3, platelet exposure to cyclic GMP-elevating agents such as sodium nitroprusside and M&B-22948 (2-o-propoxyphenyl-8-azapurin-6-one), a cGMP phosphodiesterase inhibitor, lowered Ca2+ mobilization in response to thrombin. Interestingly, when cGMP phosphodiesterases were blocked, endothelin-3 produced a dose-dependent cGMP accumulation (P < 0.001). Since endothelin-3 has been proposed to decrease the activity of Ca2+ accumulating pumps, we examined whether this latter effect could be mediated by a rise in cGMP content. Cyclic GMP decreased in a dose-dependent manner the initial rate and plateau value of the ATP-dependent 45Ca2+ uptake in platelet membrane vesicles (P = 0.006 for each). Furthermore, combined treatment with endothelin-3 and M&B-22948 or a moderate concentration of Na(+)-nitroprusside further reduced the thrombin-evoked Ca2+ discharge (P = 0.004 and 0.01, respectively), suggesting that endothelin-3 pre-exposure had reduced the amount of mobilizable Ca2+. We propose that the depletion of platelet Ca2+ stores and the reduction of Ca2+ release evoked by endothelin-3 could be due, at least in part, to the elevation of cGMP content and to a decrease in Ca2+ accumulating pump activity.

Analysis of Variance↗
PubMed1996

Nitric oxide inhibits ATP-dependent Ca2+ uptake into platelet membrane vesicles.

The reduction by nitric oxide donors of Ca2+ mobilization in stimulated platelets lead us to investigate the direct effect of authentic NO on ATP-dependent Ca2+ uptake into platelet membrane vesicles. The effects of NO were compared to those of thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone, two specific inhibitors of the sarco/endoplasmic reticulum Ca2+-ATPases. All three compounds modulated the initial rate of ATP-dependent Ca2+ uptake. NO effects on the initial rate of active Ca2+ uptake were biphasic, with an inhibition above 10 nmol/L and a stimulation below this concentration. These effects could not be attributed to cGMP, its usual effector molecule, or to nitrite ions, its metabolic product. NO inhibitory effects were decreased after a five min incubation, indicating that they were due to a short-lived compound and reversible. These results suggest that NO is functionally coupled to SERCA pumps of the dense tubular system through a cGMP-independent mechanism.

Biological Transport, Active↗
PubMed1996

Alteration of lymphocyte membrane phospholipids and intracellular free calcium concentrations in hyperlipidemic subjects.

Hypercholesterolemia has been proposed to influence cell functions via changes in membrane composition. The aim of the present study was to determine whether the membrane phospholipid composition of human lymphocytes is modified in hypercholesterolemia and whether these changes are accompanied by functional modifications. The phospholipid fatty acid contents and intracellular free calcium concentrations were determined in peripheral blood lymphocytes from 13 subjects with serum total cholesterol levels ranging from 4.6 to 8.8 mmol/l. The spontaneous basal rate of thymidine incorporation in lymphocyte of hypercholesterolemic individuals increased, while its relative stimulation by ConA was less effective. Important changes in membrane lipid composition, consisting mainly of decrease of the mass of phospholipids, and of associated polyunsaturated fatty acids were observed in hypercholesterolemia. In contrast, the cell cholesterol content was significantly increased. The intracellular free calcium concentration was enhanced and strongly associated with circulating cholesterol levels, cell cholesterol content and phospholipid fatty acids. These results indicate that hypercholesterolemia is accompanied by profound changes in lymphocyte membrane lipid composition and Ca(2+) handling.

Calcium↗
PubMed1996

Cell calcium handling and intracellular pH regulation in hereditary hypertriglyceridemic rats: reduced platelet response to thrombin stimulation.

Multiple cell membrane alterations have been described in humans and animals with various genetic forms of hypertension and/or dyslipidemia. The aim of our study was to characterize some properties of platelets and/or erythrocytes (cytosolic calcium handling, intracellular pH regulation and thrombin responsiveness) in a new model of genetic hypertension associated with hyperlipidemia-Prague hereditary hypertriglyceridemic (HTG) rats. There were no differences in basal cytosolic Ca2+ values in platelets or erythrocytes of HTG rats and control Wistar rats. Ca2+ influx into erythrocytes was also similar in HTG and control rats. In both strains Ca2+ influx correlated positively with plasma triglycerides. The slope of this relationship was less steep in HTG than in Wistar rats. Cytosolic Ca2+ response to thrombin stimulation was smaller in HTG platelets, which were also characterized by a major reduction of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels. Platelets of HTG rats had the same basal intracellular pHi values and similar buffering capacity as control rats but their pHi response to thrombin stimulation was substantially reduced. It can be concluded that reduced responsiveness to thrombin stimulation is a major alteration found in platelets of hypertensive hereditary hypertriglyceridemic rats.

Animals↗
PubMed1996

Platelet calcium handling is different in rats with salt-dependent and spontaneous forms of genetic hypertension.

Increased platelet cytosolic free calcium concentration ([Ca2+]i) has been demonstrated in both human essential hypertension and spontaneous hypertension of the rat. The present study was designed to extend the investigation on platelet Ca2+ handling to two models of salt-dependent genetic hypertension (Sabra and Dahl rat strains). No major [Ca2+]i elevation was seen in salt hypertensive SBH Sabra or SS/Jr Dahl rats. This contrasts with the data obtained in Lyon hypertensive rats (a spontaneous form of genetic hypertension) in which basal platelet [Ca2+]i was clearly increased and correlated positively with diastolic blood pressure. In these two strains, basal platelet [Ca2+]i correlated with pulse pressure but not with diastolic pressure. The absence of a significant relationship between platelet [Ca2+]i and diastolic pressure in both Sabra and Dahl rats indicates that, at least in young rats with developing salt hypertension, platelet cytosolic calcium need not reflect calcium changes occurring in the vascular smooth muscle or resistance arterioles. In contrast to the high values seen in Lyon hypertensive rats, the [Ca2+]i rise induced by thrombin was unchanged in salt-sensitive SS/Jr Dahl rats and substantially reduced in hypertension-prone SBH rats (irrespective of salt intake). The initial rate of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels was similar in SBN and SBH as well as in SR/Jr and SS/Jr rats kept on a low-salt diet but was reduced by high salt intake in platelets of salt-resistant (SBN and SR/Jr) animals only. Since platelets of Lyon hypertensive rats are also characterized by greater initial rate of thrombin-induced Mn2+ entry, this parameter was always higher in rats with established hypertension compared to their respective normotensive controls. Our study demonstrated that alterations of platelet Ca2+ handling are different in salt-dependent than in spontaneous forms of genetic hypertension.

Animals↗
PubMed1996

SK&F 96365 inhibits intracellular Ca2+ pumps and raises cytosolic Ca2+ concentration without production of nitric oxide and von Willebrand factor.

The effects of the imidazole compound SK&F 96365 on Ca2+ movements and production of nitric oxide (NO) and von Willebrand factor (vWF) have been investigated in human endothelial cells. Changes in cytosolic Ca2+ concentration ([Ca2+]i) were measured with Fura-2. Real-time production of NO was monitored with a porphyrinic microsensor and the release of vWF with an enzyme-linked immunosorbent assay. Irrespective of the transmembrane Ca2+ gradient, 30 microM SK&F 96365 doubled [Ca2+]i suggesting a Ca2+ release from intracellular stores. The SK&F 96365-induced [Ca2+]i rise was not accompanied by detectable NO and vWF production, while 1 microM thapsigargin enhanced [Ca2+]i 2.5 times, doubled the secretion of vWF and increased the NO production to 10 +/- 4 nM (n = 5). Pretreatment with SK&F 96365 prevented thapsigargin from increasing [Ca2+]i, NO production and vWF secretion. To investigate the mechanism by which SK&F 96365 released Ca2+ from internal pools, its effect and that of thapsigargin on the ATP-dependent 45Ca2+ uptake into platelet membrane vesicles were compared. SK&F 96365 as thapsigargin, dose-dependently reduced the initial rate of 45Ca2+ uptake. In conclusion, we demonstrate that, in the absence of Ca2+ entry from the extracellular space, the [Ca2+]i increase elicited by SK&F 96365 or thapsigargin is not sufficient to initiate NO synthesis and vWF secretion. This confirms the important role of Ca2+ influx in endothelial secretion processes.

Adenosine Triphosphate↗
PubMed1996

Enhanced phospholipase A2 activity in cultured cardiomyocytes from newborn spontaneously hypertensive rat.

1. Changes in membrane lipid composition and metabolism could participate in myocardial membrane dysfunction in essential or experimental hypertension. Phospholipid-bound fatty acid profile and metabolism are altered in cultured heart myocytes of newborn genetically hypertensive rats. The present study was designed to investigate the participation of phospholipase A2 in these modifications. 2. Phospholipase A2 activity of cultured cardiomyocytes of neonate spontaneously hypertensive rats and normotensive control Wistar-Kyoto rats was compared. The enzyme activity was measured using 2-[1-14C]arachidonyl-phosphatidylethanolamine as substrate. In both strains, Ca(2+)-dependent and independent phospholipase A2 activities were present. Only the Ca(2+)-dependent enzyme activity was altered in spontaneously hypertensive rat cardiomyocytes. With 0.2 mmol/l substrate and 5 mmol/l Ca2+, the phospholipase A2 activities were 79.0 +/- 13.4 and 26.0 +/- 3.6 nmol h-1 mg-1 of protein in spontaneously hypertensive and Wistar-Kyoto rat cardiomyocytes respectively (n = 10 in both cases, P = 0.001). The maximum velocity of the enzyme was three times higher in spontaneously hypertensive rat than in Wistar-Kyoto rat, without changes in the apparent affinity of the enzyme for its substrate. 3. The present results demonstrate an enhanced phospholipase A2 activity in cultured heart muscle cells of spontaneously hypertensive rats, which could be genetically determined.

Animals↗
PubMed1996

Influence of authentic nitric oxide on basal cytosolic [Ca2+] and Ca2+ release from internal stores in human platelets.

1. Nitric oxide (NO) donors inhibit platelet function and Ca2+ mobilization evoked by different agonists. This led us to investigate the direct effects of authentic NO on basal cytosolic Ca2+ concentration ([Ca2+]i) and on Ca2+ mobilization induced by thrombin or by two inhibitors of intracellular Ca(2+)-ATPases, thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone (t-BuBHQ). 2. Cytosolic Ca2+ concentration was evaluated with Fura-2, in the absence of Ca2+ influx. Addition of 5 microM NO increased by 48% the basal cytosolic [Ca2+] of resting human platelets whereas a lower concentration (0.1 microM) did not induce significant modifications. This NO-induced Ca2+ increase was inversely correlated with the basal level of cytosolic [Ca2+]. 3. NO pretreatment for 30 to 120 s decreased by 42 to 57% the transient [Ca2+]i peak evoked by 0.10 u ml-1 thrombin and strongly attenuated the initial rate of [Ca2+]i rise induced by 1 microM thapsigargin or by 20 microM t-BuBHQ. The two components of the thapsigargin response, the Ca2+ release due to inhibition of Ca2+ pumps and the thromboxane A2-dependent self-amplification mechanism, were inhibited by NO. The observation that a subsequent stimulation was still capable of eliciting Ca2+ release suggests the presence of NO-insensitive Ca2+ stores. 4. These findings indicate that nitric oxide can modulate basal cytosolic [Ca2+] in unstimulated human platelets and decrease the Ca2+ mobilization from NO-sensitive internal stores evoked by stimulation of receptors or by Ca(2+)-ATPase inhibitors. This underlines the important role of nitric oxide in the modulation of platelet Ca2+ handling.

Adult↗
PubMed1996

Abnormal regulation of cytosolic calcium and pH in platelets of Sabra rats in early phases of salt hypertension development.

Platelet cytosolic free calcium concentration ([Ca2+]i) and pH (pHi) have been reported to be altered in both human essential and rat spontaneous hypertension. The aim of our study was not only to search for the occurrence of such alterations in platelets of rats with salt-induced hypertension but also to investigate whether these changes might precede blood pressure rise in this form of experimental hypertension. Using fluorescent probes fura-2 and BCECF, basal values and thrombin-induced changes of [Ca2+]i and pHi were determined in platelets of young hypertension-prone (SBH) and hypertension-resistant (SBN) Sabra rats fed either low-salt (0.3% NaCl) or high-salt (4% NaCl) diets. Under the conditions of low salt intake, basal [Ca2+]i values were similar in SBH and SBN rats, whereas pHi was significantly lower in SBH than in SBN animals. Thrombin induced smaller [Ca2+]i elevation but greater pHi rise in SBH rats compared with SBN animals. The initial rate of thrombin-induced Mn2+ entry, which reflects the opening of a particular subclass of thrombin-operated Ca2+ channels, was similar in both strains. The moderate hypertension elicited in SBH rats by high salt intake was not associated with major alterations of basal [Ca2+]i or pHi values. High salt diet feeding did not influence [Ca2+]i and pHi responses to thrombin in either strain. In contrast, high salt intake reduced thrombin-induced Mn2+ entry in SBN but not in SBH rats. Basal platelet [Ca2+]i values correlated positively with systolic but not with diastolic blood pressure. This could be ascribed to a very close relationship of basal [Ca2+]i values with pulse pressure. The abnormalities of [Ca2+]i and pHi handling in platelets of Sabra rats with salt-dependent genetic hypertension differ from those described in essential hypertensive patients or rat strains with spontaneous forms of genetic hypertension. Our study also indicated that alterations of platelet [Ca2+]i do not precede blood pressure elevation in salt hypertension.

Animals↗
PubMed1995

Direct measurement of nitric oxide production in platelets: relationship with cytosolic Ca2+ concentration.

NO production in platelets has been followed by electrochemical detection. It was undetectable in unstimulated platelets and in thrombin or ADP-stimulated platelets, but dose-dependently stimulated by collagen. A production of 5 10(-19) mol/platelet was reached with 9 micrograms collagen. In collagen-stimulated platelets, preincubation with 1 mM L-Arg, D-Arg or L-NMMA increased by 77%, left unchanged or decreased by 63% NO production, respectively. NO production did not parallel cytosolic Ca2+ changes, although it decreased in low Ca2+ medium or when Ca2+ transients were attenuated by intracellular Ca2+ buffer. These results confirm that human platelets can generate NO. They demonstrate that cytosolic [Ca2+], although participating in the regulation of its synthesis, is not the messenger for NO synthase activation. Platelet NO production could become functionally important when collagen fibrils of the sub-endothelium are accessible.

Adenosine Diphosphate↗
PubMed1995

Endothelin-3 reduces Ca(2+)-uptake and Ca2+ content of platelet internal stores.

In stimulated platelets, endothelin-3 (ET-3) has been previously shown to attenuate Ca2+ mobilization. Using the calcium indicator chlortetracycline, the present study demonstrates that 0.5 microM ET-3 produced a 24% reduction in the Ca2+ pool mobilized by A23187. ET-3 up to 1 microM dose-dependently decreased the initial velocity and steady state value of 45Ca(2+)-uptake into platelet membrane vesicules (p < 0.001). In addition, ET-3 partially reversed the inhibitory effects of half maximally effective concentrations of thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone, two specific inhibitors of the sarco/endoplasmic reticulum Ca(2+)-ATPases. These results suggest that ET-3 is functionally coupled to Ca(2+)-pumps of the dense tubular system. Based on these findings, we propose that ET-3 decreases the activity of Ca(2+)-pumps in the dense tubular system which accumulates less Ca2+, leading to lowered Ca2+ release in response to agonists.

Analysis of Variance↗
PubMed1995

Isradipine affects histamine-induced cytosolic Ca2+ movements in human endothelial cells.

Although endothelial actions of dihydropyridines remain controversial, isradipine has been observed to exert anti-atherosclerotic actions in which endothelium could be involved. This study was designed to investigate the direct effects of isradipine on cytosolic Ca2+ concentration in cultured human umbilical vein endothelial cells. Isradipine (from 10 nM to 1 microM) had no effect on unstimulated cells but dose-dependently decreased both the transient [Ca2+]i peak and the sustained increase induced by histamine. Its maximal effects were reached at 0.1 microM. In the absence of Ca2+ influx or in depolarized cells, 1 microM isradipine still significantly decreased the transient [Ca2+]i peak (by 23 +/- 8% and 42 +/- 11%). Ca2+ influx induced by re-establishment of transmembrane Ca2+ gradient was also inhibited by isradipine, as was that induced by 1 microM thapsigargin. These results demonstrate that isradipine is able to reduce both Ca2+ release from internal stores and the consequent Ca2+ entry in stimulated human endothelial cells.

Calcium↗
PubMed1995

Refilling state of internal Ca2+ stores is not the only intracellular signal stimulating Ca2+ influx in human endothelial cells.

To further analyse the role of the refilling state of internal Ca2+ pools in the stimulation of Ca2+ influx in human endothelial cells, we investigated the combined effect of thapsigargin (TG) and histamine on cytosolic Ca2+ concentration ([Ca2+]i) and inositol polyphosphate production. At normal extracellular Ca2+ levels, TG induced a progressive and sustained elevation in [Ca2+]i which was dose-dependently prevented by pretreatment with 1-10 microM histamine. Similarly, pretreatment with 0.1 and 1 microM TG suppressed histamine-induced Ca2+ transients partially and totally, respectively. TG pretreatment did not alter the inositol triphosphate (IP3) level liberated by histamine, but modified IP3 metabolism by decreasing inositol biphosphate (IP2) and increasing inositol monophosphate (IP1) contents. In the absence of Ca2+ influx, 1 microM TG only induced a small transient increase in [Ca2+]i whereas the Ca2+ mobilization evoked by 10 microM histamine was unchanged. In both cases, the absence of any additional effect of either TG, histamine or 2 microM ionomycin indicated the complete depletion of Ca2+ stores. The re-establishment of the transmembrane Ca2+ gradient induced a transient rise in [Ca2+]i. Its amplitude differed between histamine- and TG-treated cells. It was imposed by cell pretreatment and was selectively affected by changes in the membrane potential. At 5 mM external K+, the transient rise in [Ca2+]i was more marked in histamine- than in TG-stimulated cells; this difference was suppressed by TG pretreatment. The presence of 130 mM external K+ increased Ca2+ entry in TG-treated cells but reduced it in histamine-stimulated cells. These results indicate that the refilling state of internal Ca2+ stores does not constitute the single regulator of Ca2+ influx. TG and histamine seem to activate Ca2+ influx through distinct but interdependent pathways regulated by membrane potential.

Calcium↗