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Increasing evidence indicates that membrane protein function can be affected by the surrounding membrane bilayer. A new study on voltage-gated potassium channels using tarantula toxins suggests that lipid interaction with the voltage sensor can influence channel function.

This paper explores how voltage-gated potassium channels can plug the pore to prevent the conductance of ions during inactivation.

Trimeric P2X receptor channels are activated by ATP and function in neural signaling, pain transmission and inflammation-based pathways. Cysteine scanning analysis of the transmembrane regions revealed that the second domain lines the central ion-conductance pore and acts like a gate to limit ion flow in the closed state.

The prevailing view for purinergic P2X receptor channels is that their ion conduction pores dilate upon prolonged activation. This study finds that the hallmark shift in equilibrium potential observed with prolonged channel activation does not result from pore dilation, but from time-dependent alterations in the concentration of intracellular ions.

Cavernous chambers, intricate passages, a gate with a curious lock — the structure of an ATP-activated ion channel reveals its architecture. And this intriguing interior design is found in another type of ion channel too.

A recent X-ray structure revealed the closed state of a P2X receptor ion channel. Here, Li and colleagues probe the structural rearrangements that take place during channel opening by measuring the effects of covalent modification of engineered cysteines.

The exploration of voltage-gated potassium channels using cryo-electron microscopy and electrophysiology identifies a mechanism of inactivation involved in regulating neuron firing.

Voltage-activated ion channels contain S1–S4 domains that endow them with exquisite voltage sensitivity. X-ray crystal structures provided a major breakthrough in elucidating the mechanistic basis of voltage sensing, revealing a helix-turn-helix motif termed the voltage-sensor paddle. A study in this issue demonstrates that this motif exists in the open state of Kv channels when embedded in native biological membranes and puts forward new ideas about its functional role in the mechanism of voltage sensing.

The Kv1.3 potassium channel is expressed abundantly on activated T cells and mediates the cellular immune responses. Here, the authors report structures of the Kv1.3 potassium channel with and without immunoglobulin modulators, shedding light on the mechanisms of Kv1.3 gating and modulation.

One of two papers that demonstrates the importance of the lipid-exposed 'paddle' motif in voltage-dependant ion channels by showing that paddle function can be faithfully conserved when transplanted into distantly-related channels. The work also underscores the mobility of this motif within the membrane.

Despite the growing number of X-ray crystal structures of membrane proteins, direct structural information about proteins in their native membrane environment remains scarce. Neutron diffraction, solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations are now used to investigate the structure and hydration of bilayer membranes containing S1–S4 voltage-sensing domains.

Enzymatic conversion of sphingomyelin to ceramide-1-phosphate in the external leaflet of the cellular membrane has now been shown to markedly facilitate opening of classical voltage-activated potassium channels. This discovery raises the possibility that lipids may have more prominent roles in the gating mechanism of these important ion channels than was previously appreciated.

Structural studies of potassium channels suggest that opening of the gate involves large changes in the intracellular pore aperture, leaving a pore diameter >12 Å. A recent mechanistic study on eukaryotic voltage-activated potassium channels points to an alternative picture of opening, including a smaller open pore and possibly a unique hinge or swivel point.