In cardiac pacemaker cells, AMPK activation by AMP in low-energy conditions reduces the I_f current and slows cardiac rate, an energy-saving mechanism. This work shows that AMPK inhibits HCN4 membrane expression by direct channel phosphorylation, and shows that this process contributes to age-dependent intrinsic rate slowing.

Electrical synapses enable neural circuits to perform as coincidence detectors, that is, to preferentially respond to simultaneous inputs. The temporal precision of this operation is critically determined by voltage-dependent conductances of the soma and proximal axon.

Sun et al. show that the commonly used Ca_V3 T-type channel-selective antagonists, ML218 and Z944, modulate the activity of Ca_V1.4 L-type channels through a mechanism involving the dihydropyridine-binding site.

Nguyen et al. show that Arg-92 in GIRK2 is essential for PIP2-dependent gating, with substitutions causing structural rearrangements that disrupt G protein and alcohol activation—likely a conserved mechanism among inward rectifier potassium channels.

Lopez-Mateos et al.’s study demonstrates AlphaFold2’s potential to sample multiple states of human NaV channels. Additionally, NaV α-subunit interactions with β-subunits and calmodulin reshape NaV α-subunit conformational landscape. This study reveals the potential of deep learning methods to model structural diversity of ion channels.

KdpFABC is a unique potassium pump that combines channel-like selectivity with ATP-driven transport. Using simulations, X-ray scattering, and biochemical assays, this study shows that its inter-subunit tunnel is mainly water-filled and has a single stable potassium site. The findings challenge the idea of a continuous ion-wire and highlight a key barrier at the KdpA–KdpB interface.

Channel gating in cyclic nucleotide-binding domain (CNBD) channels has traditionally been described using allosteric models. This work by Lin and Chanda compares different gating models to account for the diverse gating phenotypes observed across the CNBD family, including those arising from targeted mutations and chimeragenesis.