Patch clamp studies of lymphocyte activation.
In both T- and B-lymphocyte activation, antigen receptor or mitogen stimulation results in phosphoinositide turnover, generation of InsP3 and diacylglycerol, and a sustained rise in intracellular Ca2+, from both intracellular Ca2+ stores release and enhanced transmembrane Ca2+ influx. There is also an associated K+ efflux and membrane hyperpolarization. Patch clamp studies in T and B cells have revealed the presence of several types of ion channels that apparently contribute to the ion fluxes and to the membrane potential changes associated with lymphocyte activation. Three types of T-cell channels are described in this review. First, patch clamp studies have revealed the presence of a nonvoltage-gated, Ca2+ permeable channel, the probability of whose opening increases upon exposure of the T cell to activating ligands. Enhanced opening probability appears to be mediated by the second messenger InsP3, implying that InsP3 is responsible for both intracellular Ca2+ stores release and enhanced transmembrane Ca2+ influx. Thus, the control of [Ca2+]i remains coupled to TCR/CD3 function. The Ca2+ permeable channel also undergoes a Ca2(+)-dependent inactivation process in an autoregulatory fashion. In addition, voltage-gated K+ channels, which closely resemble the delayed rectifier K+ channel of nerve and muscle, can be classified into three subtypes, according to their voltage dependence of activation, inactivation kinetics, and pharmacological sensitivity. The expression of the three K+ channel subtypes varies with the cell's developmental state and functional class. The voltage-activated K+ channel is postulated to have a role in mitogenesis, based on studies that demonstrate an increase in K+ channel amplitude in the 24-48 hr following mitogen stimulation, and on studies that demonstrate that K+ channel blockers inhibit mitogenesis in a dose-dependent manner with the same potency sequence for ion channel block. The precise functional role of the voltage-activated K+ channel remains to be determined. Finally, a Ca2(+)-activated K+ channel in T cells has recently been described. This channel presumably underlies the K+ efflux and membrane hyperpolarization that accompany the mitogen-induced increase in [Ca2+]i. Three channel types that may contribute to activation have also been described in B lymphocytes. In murine myeloma and hybridoma cells, a voltage-gated Ca2+ channel similar to Ca2+ channels in nerve, heart, and muscle is present. It is unclear whether or not this type of Ca2+ channel is present in straight B-cell lines.(ABSTRACT TRUNCATED AT 400 WORDS)
Gardner
P
P
Department of Medicine, Stanford University, California 94305.
D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008564:Membrane Potentials; D013601:T-Lymphocytes / Q000276:immunology
D007473:Ion Channels