ADAM23 is a negative regulator of Kv1.1/Kv1.4 potassium currents

Background ADAM22 and ADAM23 are transmembrane proteins that bind the secreted synaptic protein LGI1 and associate with K(v)1.1/K(v)1.4 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 K(v)1.1/K(v)1.4. Voltage-gated potassium currents were measured by whole-cell patch-clamp. Immunostaining K(v)1.1 with fluorescent antibodies and fluorescently tagged K(v)1.1 subunits was used to measure the effects of ADAM proteins on cell-surface and total expression of K(v)1.1 channels. LGI1-conditioned media was added to assess the effect on LGI1 on K(v)1.1 currents. Results Cells transfected with K(v)1.1/K(v)1.4 showed voltage-gated potassium currents (Kv1.1 currents). ADAM23 was a powerful negative regulator of K(v)1.1 currents and caused decreased surface expression of K(v)1.1 subunits. This decrease in current was not mediated by clathrin-dependent endocytosis. LGI1-conditioned media did not affect the negative regulation of K(v)1.1 currents by ADAM23. ADAM22 had no significant effect on K(v)1.1 currents by itself, but in the presence of LGI1-conditioned media markedly potentiated K(v)1.1 currents without changing channel activation kinetics. Conclusions ADAM22 and ADAM23 have opposite effects on K(v)1.1 currents. The relative expression of these proteins, and the availability of LGI1 may shape the expression of K(v)1.1 currents in different neuronal membrane domains.