Gating Properties and Voltage Sensing in Kv1.2

Abstract

Kv1.2 is a voltage gated potassium channel whose crystal structure has been solved. There is markedly little electrophysiological information about it, which limits the vast potential usefulness of the structure. In an effort to deepen our functional understanding of the Kv1.2 channel, we set out to characterize its properties through recordings of macroscopic and single ionic and gating currents and develop models for activation based on established models for other Shaker channels. Preliminary data indicate that even though Shaker and Kv1.2 are closely related, subtle differences exist in their mechanisms of voltage sensing. As an example of these differences, limiting slope analysis reveals that the apparent charge coupled to gating of Kv1.2 is only 10 e0 compared to Shaker's 13 e0. Also, substitution of Kv1.2's tryptophan at position 366, the analogue of W434 in Shaker, for the other two aromatic residues does not abolish conduction as in Shaker. Our macroscopic data are best fitted by a 32 state model involving three independent transitions for each of the subunits and two final, voltage independent, concerted transitions to the open state.These findings make apparent the need for more detailed electrophysiological analysis of Kv1.2 and will certainly prove useful to clarify the structure-function relationship of voltage gated potassium channels.