Potassium channels are integral membrane proteins selectively permeable for potassium ions, which are expressed in all types of cells. The channels are primarily involved in regulation of electrical activity in neurons. Moreover, they are required for many different processes including cell proliferation, volume regulation, apoptosis, insulin sensitivity. The channel activity is modulated by a number of chemical factors, among them are zinc (Zn) and copper ions (Cu). In the present study we applied the electrophysiological technique "patch-clamp" in the "whole-cell" configuration to study the modulatory effect of Zn and Cu on voltage-gated potassium channels Kv1.3 expressed in human lymphocytes. Obtained results provide evidence that both Zn and Cu inhibit the activity of Kv1.3 channels when applied at micromolar concentrations by direct binding to binding sites on the channels. However, the mechanisms of such an inhibition seem to be different. First, because Cu inhibits the channels much more potently than Zn. Second, the binding stoichiometry of Cu and Zn is apparently different from each other. Moreover, the inhibition of Zn is accompanied by a significant shift of voltage-dependence of both activation and inactivation towards positive membrane potentials and by a pronounced slowing of the current activation. In case of Cu-induced inhibition, only a slowing of the current activation was observed. The inhibitory effect of Zn depends on the membrane holding potential and on extracellular potassium concentration - no such dependencies occur in case of the inhibition by Cu. The inhibition by Cu is time-dependent, whereas the Zn-induced inhibition is not. Finally, the inhibitory effects of Cu and Zn are additive. This strongly suggests that the effects occur by different mechanisms. Possible influence of these effects on the function of Kv1.3 channels is discussed.

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