Voltage-dependent ion channels in T-lymphocytes

Abstract

The gigaohm seal ‘patch-clamp’ technique has recently enabled exploration of the electrical properties of cells of the immune system. In this paper we review progress made to date in cataloguing the ion channels present in the cell membranes of T-lymphocytes and present new data on the types of ion channels present in a number of human and murine T-cell-derived cell lines. The ion channels thus far described in these cells are strikingly similar to those found in nerve and muscle cells. Voltage-gated potassium channels resembling delayed rectifier potassium channels in excitable cells are present in most T-lymphocytes, T-lymphocyte-derived cell lines and macrophages. Sodium channels indistinguishable from those in excitable cells are present in a small fraction of T-cells and T-cell lines, and in some natural killer cells. Calcium channels have been reported in B-lymphocyte-derived cell lines, but have not been found in T-lymphocytes or in any T-cell-derived cell line. Potassium channels are required for activation of T-lymphocytes by mitogen, allogeneic cells, or by antigen, for lysis of target cells by natural killer cells, and may be involved in the triggering mechanism for activation of T-cells. The prevailing conception of early events in T-lymphocyte activation, the ‘calcium hypothesis’, involves an elevation of cytoplasmic free calcium levels as the proposed ‘second messenger’ in activation, giving rise to a cascade of subsequent events resulting eventually in cell division. A major focus of this paper is to evaluate specific mechanisms which have been proposed to account for experimental evidence, both in the literature and also presented here, pertaining to the calcium hypothesis. One such mechanism involves calcium channels, which have been postulated to account for the early calcium influx in activated T-lymphocytes. Since calcium channels have not been detected in T-cells, we explore the possibility that existing data can be accounted for without calcium channels. In particular, we show that many of the effects of ‘calcium channel antagonists’ such as verapamil, nifedipine, diltiazem and some polyvalent cations, can be accounted for by their blocking of voltage-gated potassium channels.