Reflections on recent work providing mechanistic insight into the pathological effects of a cardiac troponin T mutation.
Melzer highlights new work confirming that the sarcoplasmic reticulum transmembrane voltage changes little during Ca2+ release
Pierce examines new work revealing that calnexin controls the biogenesis of ERG-type K+ channels in Caenorhabditis elegans.
Milestone in Physiology
Carriers, exchangers, and cotransporters in the first 100 years of the Journal of General Physiology
Jennings reviews the many contributions of JGP articles to our current understanding of solute transporter mechanisms.
Hansen et al. review recent structural data that have provided insight into the function and allosteric modulation of NMDA receptors.
Established models of vesicular docking/release sites can account for synaptic depression. By incorporating a separate predocked state and by assuming that docking site occupancy is <1 at rest, Pulido and Marty extend previous models and explain facilitating and nonmonotonic synaptic responses.
Nociceptors prevent damage by being able to detect and transmit noxious stimuli, such as hot temperatures. Touska et al. show that the TTX-resistant NaV channels, NaV1.8 and NaV1.9, are required for heat-resistant nociceptors to encode noxious heat and that the current through NaV1.9 increases at higher temperatures.
Duplex signaling by CaM and Stac3 enhances CaV1.1 function and provides insights into congenital myopathy
CaV1.1 is essential for initiating skeletal muscle contraction. Niu et al. demonstrate that both CaM and stac3 enhance trafficking and gating of CaV1.1. Stac3 mutations associated with congenital myopathy, weaken its binding of CaV1.1, and thus reduce trafficking.
The sarcoplasmic reticulum membrane contains ion channels, but it is unknown whether it experiences voltage changes during cellular activity. By expressing voltage-sensitive fluorescence biosensors in this membrane, Sanchez et al. suggest that it remains electrically silent during muscle activation.
A natural splice deletion of rat α-ENaC was previously reported to produce reduced ENaC current that was not attributable to reduced surface expression. Kota et al. show that this ENaC variant resists furin cleavage, implicating α-ENaC residues 34–82 in ENaC posttranslational processing.
A forward genetic screen identifies chaperone CNX-1 as a conserved biogenesis regulator of ERG K+ channels
The mechanism underlying the biogenesis of hERG channels is not fully understood. Bai et al. identify CNX-1 as a novel regulator of ERG K+ channel biogenesis that is conserved from Caenorhabditis elegans to humans.
Minimal molecular determinants of isoform-specific differences in efficacy in the HCN channel family
HCN channels generate rhythmic firing patterns in the brain and heart. Alvarez-Baron et al. identify key amino acids responsible for functional differences between cAMP-sensitive and insensitive HCN isoforms, revealing their role in communication between the nucleotide-binding domain and the pore.
There exist many different ion channel modulators that inhibit channel function, but few that increase it. Liin et al. tested 18,000 compounds by high-throughput electrophysiology and found several channel openers with a biaryl-sulfonamide motif that acts on the voltage-sensing machinery.