Naseem et al. show that the Cm28 peptide found in scorpion venom is a potent inhibitor of the K_V1.2 and K_V1.3 K⁺ channels. Cm28 is a pore blocker that obeys a unique primary structure with only 27 amino acid residues and the lack of the functional dyad characteristic of other α-KTx peptides.

De Jesús-Pérez et al. show that a reciprocal regulation between key gating elements and permeant anions sets the calcium and voltage sensitivities and the anion selectivity of the calcium-activated chloride channel TMEM16A.

Spontarelli et al. show that Y780, a disease-relevant residue in the sodium pump’s sodium-exclusive ion-binding site, stabilizes sodium binding there through a hydrogen bond, without the participation of cation–π interactions and controls K⁺ interaction at the other two ion-binding sites indirectly through a hydrogen-bond network.

Combining electrophysiology and kinetic modeling, Brake et al. highlight the role of closed-state inactivation in the gating behavior of cardiac, skeletal muscle, and neuronal voltage-gated sodium channels.

Godellas and Grosman revisit the use of ligand-binding assays to study pentameric ligand-gated ion channels (pLGICs). They show that ligand-binding affinity is unaffected by binding-site occupancy and that changes to the transmembrane domain are unlikely to affect binding to the extracellular domain.

Arachidonic acid (AA) is a known modulator of ASICs. Klipp and Bankston examine the structural requirements for ASIC modulation by a number of lipids related to AA. Negatively charged head groups are stronger potentiators and may interact with an arginine in TM1 near the outer leaflet of the plasma membrane.

Benndorf et al. present a strategy to analyze the functionality of heteromeric ligand-gated ion channels by combining subunit concatenation, mutagenesis, and extensive global fit strategies with intimately coupled Markov models.