Lithium has long been used in the treatment of psychiatric disorders. Although the mechanism of the therapeutic action of this monovalent cation have been widely studied, little is known about its effect on the AMPAR channels that underlie a majority of fast excitatory transmission at central synapses. Using the patch-clamp technique we have examined acute effects of Li-+ on single AMPAR channels in excised patches from CA1 pyramidal cells in hippocampal slices. In these cells, application of 20 mM glutamate elicits currents which predominantly reflect AMPAR channel openings. Application of 10 mM Li-+ significant enhances the size of this current. Analysis of single channel openings by time-course fitting revealed that Li-+ does not change the kinetic properties of single AMPAR channel currents and causes only a slight reduction in single-channel conductance. We obtained similar results in the presence of the AMPAR blocker Sym 2206, which reduce the number of AMPAR openings without changing the kinetic properties of single- channel currents. Our observations would be consistent with the view that the enhanced activity in the presence of Li-+ cannot be accounted for by an increase in single-channel conductance, or a change in open period. Rather, our data suggest that AMPAR potentiation by Li-+ arises from increased channel open probability.

Acknowledgement: Supported by the Wellcome Trust.