Modulation of Kv4.3 current by accessory subunits

Kv4.3 encodes the pore-forming subunit of the cardiac transient outward potassium current (I_to). hKv4.3-encoded current does not fully replicate cardiac I_to, suggesting a functionally significant role for accessory subunits. KChIP2 associates with Kv4.3 and modifies hKv4.3-encoded currents but does not replicate native I_to. We examined the effect of several ancillary subunits expressed in the heart on hKv4.3-encoded currents. Remarkably, the ancillary subunits Kvβ₃, minK, MiRP-1, the Na channel β₁ and KChIP2 increased the density and modified the gating of hKv4.3 current. hKv4.3 promiscuously assembles with ancillary subunits in vitro, functionally modifying the encoded currents; however, the physiological significance is uncertain.