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

Abstract

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.

Ca(2+)‐activated K+ channels in rat thymic lymphocytes: activation by concanavalin A.

“…Dupuis et al (1989) have, in addition, found that in cells displaying a PHA-sensitive Ca2+ current, IK(V) was inhibited probably by an increase in internal Ca2+. Bregestovski, Redkozubov & Alexeev (1986) demonstrated that IK(V) is inhibited by intracellular Ca2+ and this relationship may account for the failure of other groups to detect any reproducible effect on IK(V) in human T-cells by PHA or phorbol esters (Deutsch, Krause & Lee, 1986;Schlichter, Sidell & Hagiwara, 1986b). Our patchclamp studies showed a low density of voltage-gated K+ channels in resting rat thymocytes and no activation of this class of K+ channels by ConA.…”

Pattern of Kvβ Subunit Expression in Macrophages Depends upon Proliferation and the Mode of Activation

“…In contrast, in T lymphocytes, which express Kv␤ proteins (15), Kv1.3 inactivates with a time constant of 150 -200 ms at ϩ40mV (37), similar to that in LPS-stimulated BMDM. However, this could be as a result of the model because human T cells were activated with PHA A to increase K ϩ channel expression (37,38). Thus, Kv1.3 in BMDM and T cells inactivates faster than in HEK cells, suggesting a role for Kv␤ subunits in the leukocyte membrane excitability.…”

Calcium-activated potassium channels in resting and activated human T lymphocytes. Expression levels, calcium dependence, ion selectivity, and pharmacology.

“…In human T cells, the number of type n K(V) channels per cell increases, but the density of these channels probably remains about the same; in our experiments using T cells activated for 3-6 d, we found a 3.4-fold increase in gK00 compared with resting cells, an increase that paralleled the increase in surface area of cells selected for patch clamping in the population. Deutsch and colleagues found an increase in gK~v) of 1.7-fold for 1-and 2-d PHA-activated T ceils after mitogenic activation (Deutsch, Krause, and Lee, 1986). In mouse T cells, a relatively larger increase in the number of K(V) channels after mitogenic activation represents an increase in the density of K(V) channels; the number of these channels in resting murine T cells is lower than in resting human T cells (DeCoursey, Chandy, Gupta, and Cahalan, 1987b).…”