LAUSR

Background ADAM22 and ADAM23 are transmembrane proteins that bind the secreted synaptic protein LGI1 and associate with Kv1.1/Kv1.4 potassium channels. However, the roles of these proteins in regulated voltage-gated potassium currents are poorly understood. Methods Cultured cells were transfected to express ADAM22, ADAM23, and Kv1.1/Kv1.4. Voltage-gated potassium currents were measured by whole-cell patch-clamp. Immunostaining Kv1.1 with fluorescent antibodies and fluorescently tagged Kv1.1 subunits was used to measure the effects of ADAM proteins on cell-surface and total expression of Kv1.1 channels. LGI1-conditioned media was added to assess the effect on LGI1 on Kv1.1 currents. Results Cells transfected with Kv1.1/Kv1.4 showed voltage-gated potassium currents (Kv1.1 currents). ADAM23 was a powerful negative regulator of Kv1.1 currents and caused decreased surface expression of Kv1.1 subunits. This decrease in current was not mediated by clathrin-dependent endocytosis. LGI1-conditioned media did not affect the negative regulation of Kv1.1 currents by ADAM23. ADAM22 had no significant effect on Kv1.1 currents by itself, but in the presence of LGI1-conditioned media markedly potentiated Kv1.1 currents without changing channel activation kinetics. Conclusions ADAM22 and ADAM23 have opposite effects on Kv1.1 currents. The relative expression of these proteins, and the availability of LGI1 may shape the expression of Kv1.1 currents in different neuronal membrane domains.