Modulation of agonist-activated calcium influx by extracellular pH in rat pancreatic acini

Muallem, Shmuel; Pandol, Stephen J.; Beeker, Timothy G.

doi:10.1152/ajpgi.1989.257.6.g917

Cited by 23 publications

(27 citation statements)

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“…This inhibition is probably mediated through a direct effect of external H+ on th e apical Ca2+ influx pathway, which is supported by our previous findings th a t both apical and basolateral acidification lead to comparable decreases in intracellular pH, but only low apical pH inhibits transcellular Ca2+ transport [7]. In various cell types, including other epithelial tissues, a similar pH dependence of Ca2+ entry pathways has been described [31,32], In addition, extracellular H+ are know n to inhibit voltage-gated Ca2+ channels in excitable tissues by changing their conformation and m odifying their gating properties [33], The molecular n atu re of the epithelial Ca2+ influx pathway involved in Ca2+ reabsorption in the distal nephron has rem ained obscure so far. Several types of voltage-dependent Ca2+ channels have been described in renal distal tu b u lar cells of different species.…”

Section: Discussionsupporting

confidence: 82%

Co-ordinated control of apical calcium influx and basolateral calcium efflux in rabbit cortical collecting system

et al. 1997

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Summary Transcellular Ca2+ transport in the distal nephron involves passive Ca2+ influx at the apical membrane, diffusion through the cytosol and active extrusion across the opposing basolateral membrane. The molecular identity of the apical Ca2+ entry step is still elusive, but its regulatory aspects have been analyzed in the present study. To this end, rabbit connecting and cortical collecting tubular cells were cultured on permeable and transparent supports and the apical Ca2+ influx was deduced from Mn2+ quenching of Ca2+ independent Fura-2 fluorescence, while the intracellular Ca2+ concentration ([Ca2+],) was measured simultaneously. In parallel experiments, transcellular Ca2+ transport was determined isotopically as 45Ca2+ flux from the apical to basolateral compartment. Decreasing the apical pH from 7.4 to 5.9 inhibited transcellular Ca2+ transport by 53 ± 1%, whereas apical Ca2+ influx was reduced by 39 ± 7% and [Ca2+], decreased by 18 ± 3%. Reversal of the Na+/Ca2+ exchanger by iso-osmotic replacement of Na+ by N-methyl-Dglucamine in the basolateral compartment resulted in 50 ± 5% inhibition of Ca2* transport, 46 ± 3% reduction of apical Ca2+ influx and 60 ± 3% increase in [Ca2+]r In the absence of basolateral Ca2+, however, this manoeuvre decreased [Ca2*], by 21 ± 8%, while Ca2+ transport and apical Ca2+ influx were reduced by the same magnitude as in the presence of Ca2+, that is by 53 ± 6% and 45 ± 4%, respectively. Stimulation of adenylyl cyclase with forskolin (10-5 M) increased transcellular Ca2+ transport by 108 ± 40%, stimulated apical Cas+ influx by 120 ± 17% and increased [Ca2+]i by 110 ± 2%. In conclusion, the apical Ca2+ influx is regulated by apical pH, intracellular cAMP and basolateral Na+/Ca2+ exchanger activity, and is coupled in an 1:1 fashion to the rate of transepithelial Ca2+ transport.

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Section: Discussionsupporting

confidence: 82%

Co-ordinated control of apical calcium influx and basolateral calcium efflux in rabbit cortical collecting system

et al. 1997

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“…Slight acidification and alkalinization of external solutions results in reduction and elevation of SOC influx, respectively. Previous work performed on pancreatic acini (Muallem et al, 1989) and the epithelial colon carcinoma cell line HT 29 (Nitschke et al, 1996) have demonstrated sensitivity of Ca 2ϩ entry to acidic pH.…”

Section: Discussionmentioning

confidence: 97%

“…Since the ionization states of amino acid residues are highly dependent on pH, it is possible that acidification may result in the inactivation of second messenger mediators of SOC. In this regard, attenuation of SOC in pancreatic acinar cells by acidification is relatively independent of intracellular pH when extracellular pH is held constant, suggesting that added protons act to modulate SOC through the modification of cellular structures on the external surface of the cell membrane (Muallem et al, 1989). An alternative explanation for the reduction of SOC by extracellular acidification is the alteration of Na ϩ /H ϩ exchanger operation through either intra-or extracellular acidification (Siesjö et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of store‐operated Ca²⁺ influx by acidic extracellular pH in cultured human microglia

Khoo

Helm

Choi

et al. 2001

Glia

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The effects of extracellular acidification on Ca 2ϩ -dependent signaling pathways in human microglia were investigated using Ca 2ϩ -sensitive fluorescence microscopy. Adenosine triphosphate (ATP) was used to elicit Ca 2ϩ responses primarily dependent on the depletion of intracellular endoplasmic reticulum (ER) stores, while platelet-activating factor (PAF) was used to elicit responses primarily dependent on store-operated channel (SOC) influx of Ca 2ϩ . The duration of transient responses induced by ATP was not significantly different in standard physiological pH 7.4 (mean duration 30.2 Ϯ 2.5 s) or acidified pH 6.2 (mean duration 31.7 Ϯ 2.8 s) extracellular solutions. However, the time course of the PAF response at pH 7.4 was significantly reduced by 87% with external pH at 6.2. These results suggest that acidification of extracellular solutions inhibits SOC entry of Ca 2ϩ with little or no effect on depletion of ER stores. Changes of extracellular pH over the range from 8.6 to 6.2 during the development of a sustained SOC influx induced by PAF resulted in instantaneous modulation of SOC amplitude indicating a rapidly reversible effect of pH on this Ca 2ϩ pathway. Whole-cell patch clamp recordings showed external acidification blocked depolarization-activated outward K ϩ current indicating cellular depolarization may be involved in the acid pH inhibition. Since SOC mediated influx of Ca 2ϩ is strongly modulated by membrane potential, the electrophysiological data suggest that acidification may act to inhibit SOC by cellular depolarization. These results suggest that acidification observed during cerebral ischemia may alter microglial responses and functions. GLIA 36:22-30, 2001.

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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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Modulation of agonist-activated calcium influx by extracellular pH in rat pancreatic acini

Cited by 23 publications

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Co-ordinated control of apical calcium influx and basolateral calcium efflux in rabbit cortical collecting system

Co-ordinated control of apical calcium influx and basolateral calcium efflux in rabbit cortical collecting system

Inhibition of store‐operated Ca²⁺ influx by acidic extracellular pH in cultured human microglia

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

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Modulation of agonist-activated calcium influx by extracellular pH in rat pancreatic acini

Cited by 23 publications

References 0 publications

Co-ordinated control of apical calcium influx and basolateral calcium efflux in rabbit cortical collecting system

Co-ordinated control of apical calcium influx and basolateral calcium efflux in rabbit cortical collecting system

Inhibition of store‐operated Ca2+ influx by acidic extracellular pH in cultured human microglia

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

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Inhibition of store‐operated Ca²⁺ influx by acidic extracellular pH in cultured human microglia