[Effect of calmodulin blockers on membrane potential, potassium permeability and lymphocyte mitogenesis]

The effects of calmodulin antagonists--trifluoperazine and chlorpromazine--on the membrane potential, K+ efflux and mitogenic response of rat thymocytes and human peripheral blood lymphocytes were investigated. Phenothiazines were found to produce depolarization in both types of lymphocytes even when taken at micromolar concentrations. This effect was not caused by the inhibition of the Na+,K+-pump or by a decrease in K+ permeability of the lymphocyte membrane. The depolarization diminished in a low Na+ medium or in the presence of amiloride, an inhibitor of Na+/H+ exchange. The results obtained suggest that calmodulin is involved in the maintenance of the low level of Na+ permeability in resting lymphocytes. In thymocytes, trifluoperazine and chlorpromazine do not inhibit K+ efflux induced by A23187, hence calmodulin does not participate in the regulation of Ca2+-dependent K+-channels in these cells. Trifluoperazine (10 microM) strongly blocks the mitogenic response of blood lymphocytes. Thus, the calmodulin antagonists inhibit the mitogen-induced activation of lymphocytes.