Analysis of the K+ current in human CD4+ T lymphocytes in hypercholesterolemic state

Atherosclerosis involves immune mechanisms: T lymphocytes are found in atherosclerotic plaques, suggesting their activation during atherogenesis. The predominant voltage-gated potassium channel of T cells, Kv1.3 is a key regulator of the Ca2+-dependent activation pathway. In the present experiments we studied the proliferation capacity and functional changes of Kv1.3 channels in T cells from healthy and hypercholestaeremic patients.By means of CFSE-assay (carboxyfluorescein succinimidyl ester) we showed that spontaneous activation rate of lymphocytes in hypercholesterolemia was elevated and the antiCD3/antiCD28 co-stimulation was less effective as compared to the healthy group. Using whole-cell patch-clamping we obtained that the activation and deactivation kinetics of Kv1.3 channels were faster in hypercholesterolemic state but no change in other parameters of Kv1.3 were found (inactivation kinetics, steady-state activation, expression level). We suppose that incorporation of oxLDL species via its raft-rupturing effect can modify proliferative rate of T cells as well as the gating of Kv1.3 channels.

► We compared lymphocyte activation in normo- and hypercholesterolemic state.
► Spontaneous activation rate of lymphocytes in hypercholesterolemia was elevated.
► AntiCD3/antiCD28 co-stimulation was less effective in hypercholesterolemia.
► Activation and deactivation kinetics of Kv1.3 were faster in hypercholesterolemia.
► Incorporation of oxLDL via its raft-rupturing effect can cause the changes above.