Figure 5
From: Extracellular redox sensitivity of Kv1.2 potassium channels
Systematic mutagenesis of transmembrane cysteine residues in Kv1.2. (A) Cysteine residues are highlighted in red on the Kv1.2 structure (PDB 3LUT). C181, C229, C244, and C394 in the transmembrane domains were mutated to alanine. (B) Use-dependent activation of each cysteine mutant was assessed with trains of repetitive depolarizations, as described in Fig. 1, in ambient redox and after incubation in 666 µM DTT (N = 10–22 for each condition). (C) Schematic model depicting redox dependent interactions of Kv1.2 with a postulated extrinsic binding partner (blue) that mediates use-dependent activation. We propose that the reduced state of the regulatory partner has a high affinity for the Kv1.2 channel that promotes an inhibited gating mode by stabilizing the resting conformation. In more oxidizing conditions, the regulatory partner has weakened or altered interactions with Kv1.2, causing the inhibited gating mode to be less prominent.
