Origin of functional diversity among tetrameric voltage-gated channels.

The aim of the present work is to relate functional differences of voltage-gated K(+) (K(v)), hyperpolarization-activated cyclic nucleotide-gated (HCN), and cyclic nucleotide gated (CNG) channels to differences in their amino acid sequences. By means of combined bioinformatic sequence analyses and homology modelling, we suggest that: (1) CNG channels are less voltage-dependent than K(v) channels since the charge of their voltage sensor, the S4 helix, is lower than that of K(v) channels and because of the presence of a conserved proline in the S4-S5 linker, which is quite likely to uncouple S4 from S5 and S6. (2) In HCN channels, S4 features a higher net positive charge with respect to K(v) channels and an extensive network of hydrophobic residues, which is quite likely to provide a tight coupling among S4 and the neighboring helices. We suggest insights on the gating of HCN channels and the reasons why they open with membrane hyperpolarization and with a significantly longer time constant with respect to other channels.

Anselmi C ，Carloni P ，Torre V 《-》

Voltage-sensing mechanism is conserved among ion channels gated by opposite voltages.

Männikkö R ，Elinder F ，Larsson HP 《NATURE》

Tryptophan-scanning mutagenesis in the S1 domain of mammalian HCN channel reveals residues critical for voltage-gated activation.

Ishii TM ，Nakashima N ，Ohmori H 《-》

Solution structure of the HsapBK K+ channel voltage-sensor paddle sequence.

Unnerståle S ，Lind J ，Papadopoulos E ，Mäler L ... -  《-》

The S4-S5 linker couples voltage sensing and activation of pacemaker channels.

Chen J ，Mitcheson JS ，Tristani-Firouzi M ，Lin M ，Sanguinetti MC ... -  《-》