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Cover Image
Cover Image
ON THE COVER
Map of STIM1:Orai1 ratio from the basal surface of a transfected HEK 293A cell. Circles represent Orai1 channel clusters (puncta); STIM1:Orai1 ratio is color coded from blue (low) to red (high). Gradients in STIM1:Orai1 ratio, combined with optical and electrical recording of Orai1-GCaMP6f channel activity, reveal functional heterogeneity in Orai1 puncta and enable systematic study of STIM1-Orai1 channel states. Image © Dynes et al., 2020. See https://doi.org/10.1085/jgp.201812239. - PDF Icon PDF LinkTable of Contents
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Research News
How calcium helps α7 nicotinic acetylcholine receptors fulfill their potential
JGP study reveals that, at low acetylcholine concentrations, calcium enhances channel opening by binding to a novel motif near the ligand binding site.
Viewpoint
Roles for the SNAP25 linker domain in the fusion pore and a dynamic plasma membrane SNARE “acceptor” complex
The domain in SNAP25 that links its two SNARE motifs plays important roles in fusion pore formation, secretion kinetics, and the formation of a dynamic plasma membrane SNAP25/syntaxin “acceptor” complex for the v-SNARE synaptobrevin.
Articles
Mechanism of calcium potentiation of the α7 nicotinic acetylcholine receptor
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.
Zn2+-induced changes in Cav2.3 channel function: An electrophysiological and modeling study
Neumaier et al. reveal that Zn2+ effects on Cav2.3 channels are complex, can be either inhibitory or stimulatory, and may persist for several minutes after cessation of the Zn2+ signal. A Markov model is developed that can account for Cav2.3 channel currents in the absence and presence of physiological Zn2+ concentrations.
Cell-wide mapping of Orai1 channel activity reveals functional heterogeneity in STIM1-Orai1 puncta
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.
E1784K, the most common Brugada syndrome and long-QT syndrome type 3 mutant, disrupts sodium channel inactivation through two separate mechanisms
Inheritable and de novo variants of voltage-gated sodium channels that lead to sudden cardiac death can affect several different aspects of channel function, making pharmaceutical treatment difficult. Peters et al. show that the E1784K mutant in Nav1.5 alters channel function through two distinct and separable mechanisms.
Rational design of a mutation to investigate the role of the brain protein TRIP8b in limiting the cAMP response of HCN channels in neurons
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.
