ON THE COVER
Encoding of a photocaged serine allows for site-specific control of phosphorylation with light. CFTR channels with encoded caged serine at position 813 (lower left) are marginally activated with protein kinase A activation, but upon blue light decaging (middle), the channel becomes phosphorylated and activated (right). Image © Infield et al., 2023. Vol. 155, Issue 4. https://doi.org/10.1085/jgp.202213216.
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Phosphoinositide regulation of voltage-gated sodium channels
JGP study reveals that the membrane lipid PI(4,5)P2 alters the activity of NaV1.4 channels by modulating their gating behavior.
Blue flash sheds light on the roles of individual phosphoserines in CFTR channel activation
Light-controlled availability for phosphorylation reveals dominant roles of select R-domain serines in CFTR channel activation.
Heteromeric wild-type/mutant potassium channel subunit composition as a major determinant of channelopathy phenotype in heterozygous patients
How can AI accelerate advances in physiology?
Combining machine learning with mechanistic computational modeling is enabling the discovery of novel genotype-phenotype relationships in heart disease.
Activation of excitatory glycine NMDA receptors: At the mercy of a whimsical GluN1 subunit
Glycine-gated NMDA receptors contribute to brain functions and disorders. Rouzbeh et al. shed light on their odd pharmacology.
Allosteric modulation of GluN1/GluN3 NMDA receptors by GluN1-selective competitive antagonists
GluN1/GluN3 receptors display unusual activation properties compared to GluN1/GluN2 NMDA receptors. This study investigates mechanisms by which GluN1-selective antagonists potentiate GluN1/GluN3 responses and shows that variation in GluN1 agonist binding domain conformations promoted by antagonist binding differently modulates agonist potency and efficacy at GluN3 subunits.
Binding motif for RIC-3 chaperon protein in serotonin type 3A receptors
This work identifies a binding motif in a serotonin channel (5-HT3A) for RIC-3 protein. The discovery positions the interaction as a potential drug target in treating 5-HT3A-related disorders and opens new research directions to understand channel biogenesis.
PI(4,5)P2 regulates the gating of NaV1.4 channels
NaV channel gating is highly regulated to generate and support action potential firing in excitable tissues. In this study, optogenetic-activation of phosphoinositide-phosphatases reveals that PI(4,5)P2 levels at the membrane tune the physiological gating behavior of NaV1.4 channels.
The contribution of N-terminal truncated cMyBPC to in vivo cardiac function
Expression of N-terminal truncated cMyBPC is sufficient to modulate systolic function in vivo, demonstrating that these domains have an important functional role. Understanding of region-specific function of cMyBPC can be leveraged to manipulate various aspects of cardiac function.
BK channel modulation by positively charged peptides and auxiliary γ subunits mediated by the Ca2+-bowl site
The intracellular C-terminal positively charged regions of the γ subunits play important roles in BK channel modulation. This work identifies positively charged peptides as BK channel modulators and reveals a role for the Ca2+-bowl site in BK channel modulation by positively charged peptides and the auxiliary γ subunits.
Depressed myocardial cross-bridge cycling kinetics in a female guinea pig model of diastolic heart failure
Diastolic dysfunction was induced in guinea pigs by pressure overload. We found myofilament dysfunction that included depressed force development, reduced tension-dependent ATP consumption rate, prolonged Ktr, and prolonged myofibril relaxation in the absence of a change in myosin isoform composition. Blunted cross-bridge cycle kinetics may be an important contributor to diastolic heart failure.
Deciphering mechanically activated ion channels at the single-channel level in dorsal root ganglion neurons
Characterization of stretch-activated currents from dorsal root ganglion neurons reveals heterogeneity at the single-channel conductance level and suggests that in addition to PIEZO2, at least two other mechanically activated ion channels are expressed in somatosensory neurons.