Voltage-gated K+ channels in human T lymphocytes: a role in mitogenesis?

Abstract

Membrane receptors and ion transport mechanisms probably have an important role in lymphocyte activation leading to T-lymphocyte proliferation in the immune response. Here we have applied a gigaohm-seal patch clamp technique to reveal the identity and properties of ion channels in human T lymphocytes. A voltage-dependent potassium channel bearing a resemblance to the delayed rectifier of nerve and muscle cells was found to be the predominant ion channel in these cells. In the whole cell recording conformation, the channels open with sigmoid kinetics during depolarizing voltage steps, reaching a maximum K+ conductance of 3-5 nS. The current subsequently becomes almost completely inactivated during a long-lasting depolarization. Currents through single K+ channels recorded in whole cell and outside-out patch recording conformations reveal a unitary channel conductance of about 16 pS in normal Ringer solution. Thus, the peak current corresponds to approximately 200-300 conducting K+ channels per cell. Phytohaemagglutinin (PHA), at concentrations that produce mitogenesis, alters K+ channel gating within 1 min of addition to the bathing solution, causing channels to open more rapidly and at more negative membrane potentials. 3H-thymidine incorporation by T lymphocytes following PHA stimulation is inhibited by the 'classical' K+ channel blockers tetraethylammonium and 4-aminopyridine, and also by quinine, at doses found to block the K+ channel in voltage-clamped T lymphocytes, suggesting that K+ channels may play a part in mitogenesis.