Retinoic acid blocks potassium channels in human lymphocytes

Using the whole-cell variation of the patch-clamp technique, we have determined that retinoic acid, an active metabolite of natural vitamin A that possesses potent immunomodulating activity, reduces the K+ current in human T lymphocytes and natural killer cells in a dose-dependent manner: acute treatment with 5 X 10(-5) M caused over a 70% reduction while concentrations less than 1 X 10(-5) M caused less than 30% inhibition. Natural killer activity and T cell mitogenesis was inhibited by RA at concentrations that reduced the K+ conductance and correlated with the ability of a variety of classical ion-channel blockers to inhibit the functional activity of these cells. Thus, the reported inhibitory effects on natural killer activity and T cell mitogenesis by high concentrations of retinoic acid can be explained by its effect on the K channel.