Molecular Determinants of Selectivity for Kv1.3 K+ Channels

Molecular determinants of dofetilide block of HERG K+ channels.

The human ether-a-go-go-related gene (HERG) encodes a K+ channel with biophysical properties nearly identical to the rapid component of the cardiac delayed rectifier K+ current (IKr). HERG/IKr channels are a prime target for the pharmacological management of arrhythmias and are selectively blocked by class III antiarrhythmic methanesulfonanilide drugs, such as dofetilide, E4031, and MK-499, at ...

Ion conduction and selectivity in K(+) channels.

Potassium (K(+)) channels are tetrameric membrane-spanning proteins that provide a selective pore for the conductance of K(+) across the cell membranes. These channels are most remarkable in their ability to discriminate K(+) from Na(+) by more than a thousandfold and conduct at a throughput rate near diffusion limit. The recent progress in the structural characterization of K(+) channel provid...

Ion Conduction and Selectivity in K+ Channels

Molecular diversity of K+ channels.

K+ channel principal subunits are by far the largest and most diverse of the ion channels. This diversity originates partly from the large number of genes coding for K+ channel principal subunits, but also from other processes such as alternative splicing, generating multiple mRNA transcripts from a single gene, heteromeric assembly of different principal subunits, as well as possible RNA editi...

P-Loop Residues Critical for Selectivity in K+ Channels Fail to Confer Selectivity to Rabbit HCN4 Channels

HCN channels are thought to be structurally similar to Kv channels, but show much lower selectivity for K+. The approximately 3.3 A selectivity filter of K+ channels is formed by the pore-lining sequence XT(V/I)GYG, with X usually T, and is held stable by key residues in the P-loop. Differences in the P-loop sequence of HCN channels (eg. the pore-lining sequence L478C479IGYG) suggest these resi...