Extracellular pH modulates the Ca2+ current activated by depletion of intracellular Ca2+ stores in human macrophages

Malayev, Andrew; Nelson, Deborah J.

doi:10.1007/bf00232684

Cited by 45 publications

(42 citation statements)

References 22 publications

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“…Similarities were seen in both activation and inactivation kinetics, high sensitivity to 4-AP and relative insensitivity to TEA and DTX ( Table 2). The resemblance in the kinetics of clofilium block of I4o (Amos, Li, Wettwer, Himmel, Metzger & Ravens, 1995) and Kv1.5 channels Malayev, Nelson & Philipson, 1995) provides further evidence. Due to the sensitivity of Kv1.6 channels to TEA, DTX and CTX (Grupe et al 1990) and of I8K to La3+ (Hice et al 1994), these channels are not I4o equivalents.…”

Section: Discussionmentioning

confidence: 88%

Differences between outward currents of human atrial and subepicardial ventricular myocytes.

Amos¹,

Wettwer²,

Metzger³

et al. 1996

The Journal of Physiology

222

195

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1. Outward currents were studied in myocytes isolated from human atrial and subepicardial ventricular myocardium using the whole-cell voltage clamp technique at 220C. The Nae current was inactivated with prepulses to -40 mV and the Ca2P current was eliminated by both reducing extracellular [Ca2+] to 0 5 mm and addition of 100 /M CdCl2 to the bath solution. 2. In human myocytes, three different outward currents were observed. A slowly inactivating sustained outward current, I,,, was found in atrial but not ventricular myocytes. A rapidly inactivating outward current, It., of similar current density was observed in cells from the two tissues. An additional uncharacterized non-inactivating background current of similar size was observed in atrial and in ventricular myocytes.3. It. and I4o could be differentiated in atrial myocytes by their different kinetics and potential dependence of inactivation, and their different sensitivities to block by 4-aminopyridine, suggesting that two individual channel types were involved.4. In atrial cells, inactivation of I. was more rapid and steady-state inactivation occurred at more negative membrane potentials than in ventricular cells. Furthermore, the recovery of It. from inactivation was slower and without overshoot in atrial myocytes. In addition, 4-aminopyridine-induced block of It. was more efficient in atrial than in ventricular cells. These observations suggest that the channels responsible for atrial and ventricular It. were not identical. 5. We conclude that the differences in outward currents substantially contribute to the particular shapes of human atrial and ventricular action potentials. The existence of I.. in atrial cells only provides a clinically interesting target for anti-arrhythmic drug action, since blockers of Iko would selectively prolong the atrial refractory period, leaving ventricular refractoriness unaltered.The action potential shape shows characteristic differences between atrium and ventricle in several animal models, e.g. the guinea-pig (Hume & Uehara, 1985). Inhomogeneities in repolarizing currents between atria and ventricles generated these action potential shape differences. The action potential of human atrium is markedly shorter than that of ventricle, and possesses no clear plateau phase (Trautwein, Kassebaum, Nelson & Hecht, 1962). A careful comparison between the outward currents of human atrial and ventricular myocytes has, however, not been undertaken.The transient outward current (It.) is a major repolarizing current in both human atrium (Escande, Coulombe, Faivre,

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Section: Discussionmentioning

confidence: 88%

Differences between outward currents of human atrial and subepicardial ventricular myocytes.

Amos¹,

Wettwer²,

Metzger³

et al. 1996

The Journal of Physiology

222

195

View full text Add to dashboard Cite

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“…In addition, in preliminary experiments we found that BAPTNAM, a cell-permeant intracellular Ca2+ chelator, mediated concentration-dependent activation of caspase-3-like proteases and provided no protection against thapsigargin-mediated cell death in SH-SY5Y cells (unpublished data). BAPTA also depletes intracellular Ca2+ stores by chelating Ca2+,, which has leaked from intracellular stores and prevents refilling of the stores (Malayev and Nelson, 1995).…”

Section: Discussionmentioning

confidence: 99%

Alterations of Extracellular Calcium Elicit Selective Modes of Cell Death and Protease Activation in SH‐SY5Y Human Neuroblastoma Cells

McGinnis¹,

Wang²,

Gnegy³

1999

Journal of Neurochemistry

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Abstract:The role of intracellular Ca2+ homeostasis in mechanisms of neuronal cell death and cysteine protease activation was investigated in SH-SY5Y human neuroblastoma cells. Cells were incubated in 2 mM EGTA to lower intracellular Ca2+ or 5 mM CaCI, to raise it. Cell death and activation of calpain and caspase-3 were measured. Both EGTA and excess CaCI, elicited cell death. EGTA induced DNA laddering and an increase in caspase-3-like, but not calpain, activity. Pan-caspase inhibitors protected against EGTA-, but not CaCI,-, induced cell death. Conversely, excess Ca2+ elicited necrosis and activated calpain but not caspase-3. Calpain inhibitors did not preserve cell viability. Ca2+ was the death-mediating factor, because restoration of extracelMar Ca2+ protected against cell death induced by EGTA and blockade of Ca2+ channels by Ni'+ protected against that induced by high Ca2+. We conclude that the EGTA treatment lowered intracellular Ca2+ and elicited caspase-3-like protease activity, which led to apoptosis. Conversely, excess extracellular Ca2+ entered Ca2+ channels and increased intracellular Ca2+ leading to calpain activation and necrosis. The mode of cell death and protease activation in response to changing Ca2+ were selective and mutually exclusive, demonstrating that these are useful models to individually investigate apoptosis and necrosis. Key Words: Apoptosis-Necrosis-Calpain-Caspase-3-Ca2+ homeostasis-Neuronal death.

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“…To preclude these possibilities, we examined the effect of reducing extracellular pH on the Ca 2ϩ entry activated by thapsigargin and by arachidonic acid. Modest reductions in extracellular pH have been shown to have a profound inhibitory effect on capacitative Ca 2ϩ entry in a range of different cell types (23)(24)(25)(26), and in the case of the storeoperated channel I CRAC , this has been shown to reflect a direct action of extracellular protons on the channel (27). 2 As shown in Fig.…”

Section: Arachidonate-mediated Ca 2ϩ Entry In Hek293 Cellsmentioning

confidence: 99%

Muscarinic Receptor Activation of Arachidonate-mediated Ca2+ Entry in HEK293 Cells Is Independent of Phospholipase C

Shuttleworth

Thompson

1998

Journal of Biological Chemistry

101

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Receptor] i oscillations.Calcium signaling in non-excitable cells is composed of two components: a release of calcium from intracellular stores and an increased entry of calcium from the extracellular medium. The role of inositol 1,4,5-trisphosphate (InsP 3 ), 1 generated as a result of the receptor activation of phospholipase C, in the release of calcium from specific intracellular stores is well established, but the nature of the calcium entry pathway and its regulation is far from clear. To date, discussion of such calcium entry has generally focused on the so-called "capacitative model," in which calcium entry is activated as a direct consequence of the emptying of the intracellular calcium stores and is independent of how this emptying is actually achieved (1, 2). The precise nature of the mechanism for the activation of capacitative entry is, as yet, unclear, but it may involve the release and/or generation of a diffusible signaling molecule within the cell that activates the plasma membrane channels ("store-operated channels") responsible for calcium entry. Alternatively, a more direct molecular coupling between the stores and the plasma membrane channels may occur (3). Although such capacitative entry can be clearly demonstrated in a wide variety of different cells, it is far from certain that such a mechanism is the only one involved in the increase in calcium entry in non-excitable cells following receptor activation (4, 5). For example, many cells show an oscillatory [Ca 2ϩ ] i signal when stimulated at low agonist concentrations (6, 7), and such signals are associated with an enhanced entry of Ca 2ϩ . However, evidence indicates that the activation of capacitative Ca 2ϩ entry generally requires significantly higher levels of agonist-generated InsP 3 than does the release of Ca 2ϩ from the bulk of the agonist-sensitive internal stores (i.e. at low concentrations of InsP 3 , substantial release of Ca 2ϩ from agonistsensitive stores can occur without any activation of capacitative entry) (8 -10). Consequently, it is far from clear that the transitory (and/or incomplete) nature of calcium store depletion during [Ca 2ϩ ] i oscillations would provide an adequate or appropriate signal for the activation of calcium entry via a capacitative mechanism. Such considerations led us previously to investigate the nature of receptor-activated increases in Ca 2ϩ entry during [Ca 2ϩ ] i oscillations in cells from the exocrine avian nasal gland. In these studies, we showed that such Ca 2ϩ entry was non-capacitative in nature (11) and appeared to involve a novel arachidonate-activated pathway (12).In the experiments reported here, we extend our earlier findings to another, more widely used and functionally less highly specialized cell type, namely HEK293 cells. The specific cell line chosen had been stably transfected with the human m3 muscarinic receptor (m3-mAChR), thereby avoiding possible complications resulting from the presence of multiple muscarinic receptor subtypes. Using this cell line, we were able to s...

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Extracellular pH modulates the Ca2+ current activated by depletion of intracellular Ca2+ stores in human macrophages

Cited by 45 publications

References 22 publications

Differences between outward currents of human atrial and subepicardial ventricular myocytes.

Differences between outward currents of human atrial and subepicardial ventricular myocytes.

Alterations of Extracellular Calcium Elicit Selective Modes of Cell Death and Protease Activation in SH‐SY5Y Human Neuroblastoma Cells

Muscarinic Receptor Activation of Arachidonate-mediated Ca2+ Entry in HEK293 Cells Is Independent of Phospholipase C

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