The voltage-gated proton channel (HV1) resembles the voltage sensors of other channels, but its movement during channel opening remains controversial. Cherny et al. establish open and closed gating configurations of HV1 by analyzing the interactions of Zn2+ with an introduced histidine residue.

K+ binding to mammalian glutamate transporters is essential for the import and release of glutamate into cells. Using MD simulations and site-directed mutagenesis, Wang et al. identify two K+ binding sites in the transporter EAAC1, one of which appears to catalyze the relocation step of the transport cycle.

Stress increases the permeability of the mitochondrial inner membrane by activating permeability transition pores (PTPs), likely composed of ATP synthase or the adenine nucleotide translocator. By measuring water flux during calcium-activated mitochondrial swelling, Neginskaya et al. estimate that if these proteins are involved in PTP, only a small fraction becomes transformed into the pore on a single mitochondrion.

Mice lacking calsequestrin-1 have reduced levels of releasable Ca2+ in the sarcoplasmic reticulum of their skeletal muscles. Michelucci et al. reveal that this is compensated by constitutive assembly of STIM1 and Orai1 into Ca2+ entry units, promoting both constitutive and store-operated Ca2+ entry.

The α7 nicotinic acetylcholine receptor (nAChR) is highly abundant in the brain but is frequently located at extra-synaptic regions where the concentration of ACh is low. Natarajan et al. reveal that at low ACh concentrations, calcium potentiates α7 channel opening by binding to a novel structural motif.

The gating of neuronal HCN channels is modulated by the competitive binding of cAMP and TRIP8b, a brain-specific protein that also controls channel trafficking. Porro et al. identify a rational mutation in HCN channels that affects binding of TRIP8b, without altering cAMP affinity or TRIP8b-dependent trafficking. The mutation represents a valuable tool to investigate HCN channels in vivo.

The authors use a fluorescent genetically encoded Ca2+ indicator, GCaMP6f, fused to Orai1 to visualize Ca2+ influx through store-operated Orai1 channels. Combined with whole-cell recording of transfected human cells, this reporter reveals heterogeneity of channel activation and kinetics in STIM1-Orai1 puncta within the same cell.