Effect of lanthanum on voltage-dependent gating of a cloned mammalian neuronal potassium channel.
The effect of the trivalent cation lanthanum (La3+) 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. La3+ (100 microM) 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 La3+ 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 La3+. Furthermore, amplitudes of the inward tail currents evoked at potentials more negative than the potassium equilibrium potential (E(K+)) were more strongly inhibited by La3+ than those of the outward tail currents evoked at potentials more positive than E(K+). This suggests voltage-dependent block and binding of La3+ 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.
Tytgat
J
J
Laboratory of Toxicology, University of Leuven, Belgium. jan.tytgat@med.kuleuven.ac.be
Daenens
P
P
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003001:Cloning, Molecular; D005260:Female; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D051662:Kv1.1 Potassium Channel; D007811:Lanthanum / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000502:physiology*; D015221:Potassium Channels / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D014982:Xenopus laevis
D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051662:Kv1.1 Potassium Channel; D007811:Lanthanum