Mutations in the outer pore affecting C-type inactivation in Shaker and Kv1.2 channels

Abstract

Slow inactivation of voltage-gated potassium (Kv) channels is involved in a range of diseases including episodic ataxia and arrhythmias. Functional and structural studies have investigated the mechanism of the Drosophila Shaker Kv channel in great detail, demonstrating that a network of residue interactions behind the selectivity filter (SF) are critical for stabilizing the open state and disrupting their interactions through mutation promotes slow C-type inactivation. Since residues behind the SF between Shaker and Kv1.2 channels are highly conserved, we explored how mutations near or in the SF influence the slow inactivation of the Kv1.2 channel.