Ion channels: Gate expectations

  title={Ion channels: Gate expectations},
  author={Maria L. Garcia},
The opening and closing — gating — of ion channels in response to specific stimuli is crucial for cell function. The membrane-partitioning activities of two venom toxins give insights into the mechanisms involved. 

The gramicidin ion channel: a model membrane protein.

Direct Evidence That Receptor Site-4 of Sodium Channel Gating Modifiers Is Not Dipped in the Phospholipid Bilayer of Neuronal Membranes*

It is shown that in general, scorpion β-toxins do not partition in neuronal membranes and that in the case in which a depressantβ-toxin partitions in insect neuronal membranes, this partitioning is unrelated to its interaction with the receptor site and the effect on the gating properties of the sodium channel.

Ion channels and D-amino acids

It is interesting to note that gramicidin represents a useful model for realistic determination of conformational preference of proteins in a membrane environment, in spite of the alternating sequence of L-D chirality generally not encountered in naturally occurring peptides and proteins.

Is lipid bilayer binding a common property of inhibitor cysteine knot ion-channel blockers?

It is shown that various ICK peptides demonstrate markedly different modes of interaction with large unilamellar lipid vesicles, showing that bilayer partitioning is not a universal property of the ICk peptides interacting with ion channels.

Mechanosensitive Channels in Striated Muscle and the Cardiovascular System: Not Quite a Stretch Anymore

The role of transient receptor potential channels, several of which have been implicated as mechanosensitive channels, in the pathogenesis of adverse cardiac remodeling and as potential therapeutic targets in the treatment of heart failure are focused on.

Screening ion-channel ligand interactions with passive pumping in a microfluidic bilayer lipid membrane chip.

Dose-dependent transient blocking of α-hemolysin with β-cyclodextrin and polyethylene glycol is demonstrated and dose-dependent blocking studies of the KcsA potassium channel with tetraethylammonium show the potential for determining IC50 values.

1.2 Å X-ray Structure of the Renal Potassium Channel Kv1.3 T1 Domain

Here we present the structure of the T1 domain derived from the voltage-dependent potassium channel Kv1.3 of Homo sapiens sapiens at 1.2 Å resolution crystallized under near-physiological conditions.

Effect of graded hydration on the dynamics of an ion channel peptide: a fluorescence approach.

The results show that tryptophans in gramicidin, present in the single-stranded beta6.3 conformation, experience slow solvent relaxation giving rise to red-edge excitation shift (REES), and it is concluded that REES could prove to be a potentially sensitive tool to explore the dynamics of proteins under conditions of changing hydration.



Ion Channels And Disease

This chapter considers what is known of ion channel structure, explains the properties of the single ion channel, and shows how single-channel currents give rise to action potentials and synaptic potentials.

A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom

VSTX1, small hydrophobic poisons and anaesthetic molecules reveal a common theme of voltage sensor inhibition through lipid membrane access, consistent with the recent proposal that the sensor in voltage-dependent K+ channels is located at the membrane–protein interface.

The principle of gating charge movement in a voltage-dependent K+ channel

It is concluded that the voltage-sensor paddles operate somewhat like hydrophobic cations attached to levers, enabling the membrane electric field to open and close the pore.

Functional analysis of an archaebacterial voltage-dependent K+ channel

The functional characterization of a voltage-dependent K+ (KV) channel from a hyperthermophilic archaebacterium from an oceanic thermal vent is presented and it is shown that this channel possesses all the functional attributes of classical neuronal KV channels.

A Hot Spot for the Interaction of Gating Modifier Toxins with Voltage-Dependent Ion Channels

It is suggested that the COOH-terminal end of S3 within repeat IV contributes to forming a receptor for ω-Aga-IVA, a gating modifier toxin from spider venom that inhibits voltage-gated Ca2+ channels by shifting activation to more depolarized voltages.

Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers

The results suggest that modulation of membrane proteins by amphipathic peptides—mechanopharmacology—involves not only the protein itself but also the surrounding lipids, and the surprising efficacy of the d form of GsMTx4 has important therapeutic implications, because d peptides are not hydrolysed by endogenous proteases and may be administered orally.

Molecular Surface of Tarantula Toxins Interacting with Voltage Sensors in Kv Channels

The active surface of SGTx contains a ring-like assembly of highly polar residues, with two basic residues that are particularly critical, concentrated around a hydrophobic protrusion containing critical aliphatic and aromatic residues.

X-ray structure of a voltage-dependent K+ channel

The structure of KvAP, a voltage-dependent K+ channel from Aeropyrum pernix, is presented and a crystal structure of the full-length channel at a resolution of 3.2 Å is determined, which suggests that the voltage-sensor paddles move in response to membrane voltage changes, carrying their positive charge across the membrane.