Cytoplasmic residues influence the voltage-dependence of the gating of human K+ channels

Shaker type potassium channels are strongly voltage dependent and potassium selective. Kv1.4 channels from a variety of sources exhibit a much shallower voltage-dependence of activation than other members of the family. We have made a chimeric construct consisting of the N-terminal chain of hKv1.1 spliced onto the transmembrane portion of hKv1.4 (IN/4). When expressed in Xenopus oocytes, the chimeric channel exhibits a voltage dependence that is similar to hKv1.1 although the voltage sensing and transduction machinery presumably reside in the transmembrane portion of the channel. Loss of the N-terminal ball and chain from hKv1.4 is not responsible for this as a truncation construct, starting close to the splice junction, has the same voltage-dependence as full length hKv1.4. We suggest that residues from the N-terminal chain of hKv1.1 interact with the machinery that transduces movement of the voltage sensor into channel opening. If so, this chimeric construct could provide a handle to the identification of elements of this transduction machinery. NeuroReport 11:2913-2917 (C) 2000 Lippincott Williams & Wilkins.