ADAM23 is a negative regulator of K_v1.1/K_v1.4 potassium currents.

Background ADAM22 and ADAM23 are transmembrane proteins that bind the secreted synaptic protein LGI1 and associate with K_v1.1/K_v1.4 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_v1.1/K_v1.4. Voltage-gated potassium currents were measured by whole-cell patch-clamp. Immunostaining K_v1.1 with fluorescent antibodies and fluorescently tagged K_v1.1 subunits was used to measure the effects of ADAM proteins on cell-surface and total expression of K_v1.1 channels. LGI1-conditioned media was added to assess the effect on LGI1 on K_v1.1 currents. Results Cells transfected with K_v1.1/K_v1.4 showed voltage-gated potassium currents (Kv1.1 currents). ADAM23 was a powerful negative regulator of K_v1.1 currents and caused decreased surface expression of K_v1.1 subunits. This decrease in current was not mediated by clathrin-dependent endocytosis. LGI1-conditioned media did not affect the negative regulation of K_v1.1 currents by ADAM23. ADAM22 had no significant effect on K_v1.1 currents by itself, but in the presence of LGI1-conditioned media markedly potentiated K_v1.1 currents without changing channel activation kinetics. Conclusions ADAM22 and ADAM23 have opposite effects on K_v1.1 currents. The relative expression of these proteins, and the availability of LGI1 may shape the expression of K_v1.1 currents in different neuronal membrane domains.

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