Regulation of Sodium and Potassium Transport in Phytohemagglutinin-Stimulated Human Blood Lymphocytes

Segel, George B.; Simon, William; Lichtman, Marshall A.

doi:10.1172/jci109531

Cited by 85 publications

(33 citation statements)

References 17 publications

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“…We have previously correlated active K transport with the Na concentration in lymphocytes. An increase in Na of 1.7 times the basal concentration resulted in an increase in cell Na and K transport that was about 2.5 times the basal rate (Segel et al, 1979a). These perturbations were mimicked closely by EGTA-treated lymphocytes in which a two to threefold increase in K exodus and transport was associated with a 1.8-fold increase in cell Na.…”

Section: Discussionmentioning

confidence: 83%

The effect of calcium chelation on lymphocyte monovalent cation permeability, transport and concentration

Quastel

Segel

Lichtman

1981

Journal Cellular Physiology

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We have quantified the effect of EGTA on K exodus and uptake in human blood lymphocytes. When lymphocytes were exposed to a medium containing an EGTA concentration that resulted in an ionized Calcium (Ca) of less than 10 microM, K exodus began to increase. This increase reached nearly threefold that of the control rate in a medium containing sufficient EGTA to reduce the ionized Ca concentration below 0.1 microM. When K exodus was increased, K uptake increased proportionately. This increase in K uptake represented active transport and was associated with an 80% increase in intracellular Na concentration from 15 to 27 mM. The addition of Ca to a medium containing EGTA reversed to normal the increased K exodus and uptake. Histidine, a potent chelator of divalent cations other than Ca, had no effect on K transport. These data indicate that extracellular Ca chelation leads to an increase in lymphocyte membrane permeability and cation leak. This increased leak is associated with an elevation of the cell Na and an increase in transport to a rate equivalent to that of the exodus rate. The compensatory increase in active transport maintains the cell monovalent cation concentration within 10 to 15 mM of unperturbed levels.

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Section: Discussionmentioning

confidence: 83%

The effect of calcium chelation on lymphocyte monovalent cation permeability, transport and concentration

Quastel

Segel

Lichtman

1981

Journal Cellular Physiology

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“…According to this hypothesis, the [Na ϩ ] i would be decreased during T cell activation, because activation of the Na ϩ -Ca 2ϩ exchanger may induce the Ca 2ϩ influx as well as adequate Na ϩ effluxes. However, previous studies clearly showed that the [Na ϩ ] i significantly increased during T cell activation stimulated by lectins (18,19,32,33). This conflicted result may indicate that some mechanisms were operating during T cell activation to increase [Na ϩ ] i to maintain necessary stimulation of the reverse Na ϩ -Ca 2ϩ exchange.…”

Section: Figurementioning

confidence: 92%

An Amiloride-Sensitive and Voltage-Dependent Na+ Channel in an HLA-DR-Restricted Human T Cell Clone

Lai

Chen

Nishimura

et al. 2000

The Journal of Immunology

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We investigated changes in voltage-gated Na+ currents and effects of extracellular Na+ on proliferation in HLA-DR-restricted human CD4+ αβ T cells after stimulation with a non-self antigenic peptide, M12p54–68. In the absence of antigenic peptide, neither single (n = 80) nor APC-contacted (n = 71) T cells showed voltage-gated inward currents recording with whole-cell patch-clamp techniques, even with Ca2+ and Na+ ions present in the perfusion solution. However, with the same recording conditions, 31% (26 of 84) of APC-contacted T cells stimulated with the antigenic peptide showed voltage-dependent inward currents that were elicited from −60 mV. The inward currents were not inhibited in extracellular Ca2+-free conditions or in the presence of 1 mM NiCl2. However, they were completely inhibited in extracellular Na+-free conditions, which were made by replacing Na+ with iso-osmotic N-methyl-d-glucamine or choline. The Na+ currents were insensitive to tetrodotoxin, a classical blocker of Na+ channels, but were dose-dependently inhibited by amiloride, a potassium-sparing pyrazine diuretic. Furthermore, the Ag-specific proliferative response of T cells was completely inhibited in Na+-free Tyrode’s solution and was suppressed by amiloride in a dose-dependent manner. Our findings suggest that activation of amiloride-sensitive and voltage-gated Na+ channels would be an important step to allow an adequate influx of Na+ and maintain a sustained high Ca2+ level during T cell activation.

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“…Changes in ion content and membrane fluxes, including K+ fluxes, have been correlated with T lymphocyte activation by mitogens (Segel, Simon & Lichtman, 1979;Felber & Brand, 1983b;Deutsch, Taylor & Price, 1984). Recent work has demonstrated the presence of a voltage-gated potassium (K+) channel in human peripheral blood T lymphocytes (DeCoursey, Chandy, Gupta ; Matteson & Deutsch, 1984; and a murine cytotoxic T cell clone (Fukushima, Hagiwara & Henkart, 1984).…”

Section: Introductionmentioning

confidence: 99%

Voltage‐gated potassium conductance in human T lymphocytes stimulated with phorbol ester.

Deutsch¹,

Krause²,

Lee³

1986

The Journal of Physiology

146

111

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SUMMARY1. The whole-cell patch-clamp method was used to study the voltage-gated K+ conductance of human peripheral blood T lymphocytes.2. After entry into whole-cell recording mode, there are time-dependent changes in some properties of the conductance. Over the first 10-30 min, the threshold for activation shifts about 10 mV more negative, and the rates of activation and inactivation increase. Inactivation is less strongly voltage dependent than activation or deactivation.3. Lymphocytes were stimulated to proliferate in culture with the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA).4. No changes in K+ conductance were observed in the first few hours of TPA stimulation. 5. At 24 h after mitogen addition, TPA-treated cells were found to have 17-fold greater average voltage-gated K+ conductance than unstimulated control cells.6. At 48 h, TPA-stimulated cells had the same average K+ conductance as at 24 h, even though the cells were now much increased in size, as measured by cell capacitance.7. DNA synthesis by cultures stimulated with TPA, phytohaemagglutinin or succinyl concanavalin A was depressed by the addition of 0-1 mM-quinine at any point in the culture period. In the first 20 h after mitogen addition, DNA synthesis was more effectively inhibited by quinine than if the drug were added later. Cell proliferation was equally sensitive to quinine regardless of mitogen.

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Regulation of Sodium and Potassium Transport in Phytohemagglutinin-Stimulated Human Blood Lymphocytes

Cited by 85 publications

References 17 publications

The effect of calcium chelation on lymphocyte monovalent cation permeability, transport and concentration

The effect of calcium chelation on lymphocyte monovalent cation permeability, transport and concentration

An Amiloride-Sensitive and Voltage-Dependent Na+ Channel in an HLA-DR-Restricted Human T Cell Clone

Voltage‐gated potassium conductance in human T lymphocytes stimulated with phorbol ester.

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