Effect of lanthanum on voltage-dependent gating of a cloned mammalian neuronal potassium channel

Abstract

The effect of the trivalent cation lanthanum (La 3+) on voltage-dependent gating of a cloned mammalian neuronal Kv1.1 potassium channel was studied under whole-cell voltage-clamp conditions in oocytes of Xenopus laevis. La 3+ (100 μM) was found to decrease the potassium currents at all test potentials and to shift the midpoint of the fraction open channels/membrane voltage curve by approximately +20 mV. The opening and closing time constants of Kv1.1 channels were empirically fitted with a 4th power Hodgkin-Huxley formalism, or with mono- and multi-exponentials. It was found that La 3+ slowed down the kinetics of activation, speeded up those of deactivation, and shifted the opening kinetics by approximately +60 mV. Interestingly, all these parameters of channel gating were not affected equally by La 3+. Furthermore, amplitudes of the inward tail currents evoked at potentials more negative than the potassium equilibrium potential ( E K + ) were more strongly inhibited by La than those of the outward tail currents evoked at potentials more positive than E K + . This suggests voltage-dependent block and binding of La 3+ to the Kv1.1 channel protein. We conclude that these actions cannot be explained in terms of surface charge considerations alone. Our results provide evidence for a direct interaction with the potassium channel protein, shedding new light on the mechanism of action of this lanthanide.