Modification of sodium channel currents by lanthanum and lanthanide ions in human heart cells

Abstract

I examined the effects of 100 μM extracellular lanthanum and lanthanide ions on the fast transmembrane sodium channel currents of human heart cell segments. The experiments were conducted under control of the transmembrane electrical and chemical gradients. Lanthanum and lanthanide ion exposure decreased the amplitude and increased the inactivation time constant of the sodium current. Only a transient increase occurred for the activation time constant of the sodium current. The dependence of peak sodium current on excitatory and holding potentials (steady-state activation and inactivation curves, respectively) was transiently shifted to less negative potentials during the first 3 min of exposure, as if these cations were momentarily neutralizing the effective negative charges at the extracellular side of the membrane. The curves then returned to their original position and only the inactivation curves continued shifting progressively towards a limit at more negative membrane potentials. Membrane capacitance was always reduced and this may explain these late effects in terms of changes in membrane dielectric properties and free and bound charges, in addition to traditional screening and binding concepts. These effects were related to the electronic structure of these ions.