The TO domain of rabbit KV1.3 regulates steady state channel protein level

Abstract

The Shaker superfamily encodes voltage-gated potassium (Kv) channels. The amino (N) terminus is important for channel assembly and mediates fast inactivation. We recently isolated a Kv channel from rabbit kidney, denoted rabKv1.3 and found that deleting a region (TO domain, amino acids 3-39) proximal to the T1 recognition domain (a.a 42-185) leads to a 13-fold amplification of Kv current as compared to wild type channels. Here we show that deleting the TO domain affects neither single channel conductance nor channel open probability. Instead, it increases the absolute number of channel proteins present in the membrane. We conclude that the TO domain is a previously unrecognized Shaker Kv1.3, N-terminal regulatory region that modulates steady state channel protein density in the plasma membrane.