K channels are expressed early in human T-cell development.

Abstract

Mature human T lymphocytes proliferate in response to the mitogen phytohemagglutinin (PHA), but immature thymocytes lacking the T3 receptor (T3-thymocytes) do not. Because functioning K channels are required for proliferation of mature T cells, we asked whether immunoincompetent T3-thymocytes lack normal K channels. We report that T3-thymocytes have a K+ current similar to that of mature peripheral T cells-that is, similar voltage dependence, activation and inactivation kinetics, and pharmacology. Moreover, the maximal specific K+ conductance is the same for both cell types, implying a similar density of activable channels in each cell. In assessing the functional responses of the channels to PHA, we found that the K+ current ofimmature and mature cells responds similarly to the mitogen. Responses near the threshold voltage for activating the K+ current were variable; the K+ conductance and rate of activation were increased, decreased, or unchanged after PHA treatment. For several cells, the voltage dependence of the conductance and activation kinetics was shifted in opposite directions. At more positive voltages, PHA consistently caused a 10-20% suppression of conductance that was not due to the addition of an inward current, to changes in the time course of activation or inactivation, or to changes in the steady-state level of inactivation. The effects of PHA on the K+ current cannot be explained by a simple shift in surface potential, as has been hypothesized to be involved in its triggering of T-cell proliferation. Taken together, our findings show (i) K channels are expressed very early in T-cell differentiation, possibly before thymic processing, (i) differential responses of the K+ current to PHA do not account for the failure of T3-thymocytes to proliferate, and (iii) changes in surface potential are probably not a necessary early event in activation of T cells by PHA.

Mitogens and Oncogenes Can Block the Induction of Specific Voltage-Gated Ion Channels

“…This "constitutive" expression of these K+ channels agees with previous findings of K+ channel expression in mmature or undifferentiated cells (1,23) and contrasts with the regulated induction of functional a2+ and Na+ channels. 1A).…”

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.…”

Modulation of potassium channels in human T lymphocytes: effects of temperature.

“…Series resistance compensation was 50-70 % and the whole-cell currents were sufficiently small that errors in voltages should be less than 2 mV under all conditions. Currents were allowed to stabilize for at least 10 min before experiments began, since changes in the voltage dependence ofIK(V) occur in the first few minutes of recording (Cahalan et al 1985: Schlichter et al 1986aSchlichter, Sidell & Hagiwara, 1986b). Pipettes with resistances of 3-6 MQ were coated with either Sylgard (Dow Corning Co., MI, USA) or Sigmacote (Sigma Chemical Co., MO, USA).…”