Referenced in: Kv1.4

Automatically associated channels: Kv1.1 , Kv1.2 , Kv1.4 , Slo1

Title: N type rapid inactivation in human Kv1.4 channels: functional role of a putative C-terminal helix.

Authors: Kavitha Sankaranarayanan, Anurag Varshney, M K Mathew

Journal, date & volume: Mol. Membr. Biol., 2005 Sep-Oct , 22, 389-400

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16308273

Abstract
Voltage gated potassium channels are tetrameric membrane proteins, which have a central role in cellular excitability. Human Kv1.4 channels open on membrane depolarization and inactivate rapidly by a 'ball and chain' mechanism whose molecular determinants have been mapped to the cytoplasmic N terminus of the channel. Here we show that the other terminal end of the channel also plays a role in channel inactivation. Swapping the C-terminal residues of hKv1.4 with those from two non-inactivating channels (hKv1.1 and hKv1.2) affects the rates of inactivation, as well as the recovery of the channel from the inactivated state. Secondary structure predictions of the hKv1.4 sequence reveal a helical structure at its distal C-terminal. Complete removal or partial disruption of this helical region results in channels with remarkably slowed inactivation kinetics. The ionic selectivity and voltage-dependence of channel opening were similar to hKv1.4, indicative of an unperturbed channel pore. These results demonstrate that fast inactivation is modulated by structural elements in the C-terminus, suggesting that the process involves the concerted action of the N- and C-termini.