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Journal of General Physiology

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https://www.readbyqxmd.com/read/28720591/using-fluorescence-to-understand-%C3%AE-subunit-nav-channel-interactions
#1
Rene Barro-Soria, Sara I Liin, H Peter Larsson
No abstract text is available yet for this article.
July 18, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28720590/mechanisms-of-noncovalent-%C3%AE-subunit-regulation-of-nav-channel-gating
#2
Wandi Zhu, Taylor L Voelker, Zoltan Varga, Angela R Schubert, Jeanne M Nerbonne, Jonathan R Silva
Voltage-gated Na(+) (NaV) channels comprise a macromolecular complex whose components tailor channel function. Key components are the non-covalently bound β1 and β3 subunits that regulate channel gating, expression, and pharmacology. Here, we probe the molecular basis of this regulation by applying voltage clamp fluorometry to measure how the β subunits affect the conformational dynamics of the cardiac NaV channel (NaV1.5) voltage-sensing domains (VSDs). The pore-forming NaV1.5 α subunit contains four domains (DI-DIV), each with a VSD...
July 18, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28720589/dynamic-role-of-the-tether-helix-in-pip2-dependent-gating-of-a-g-protein-gated-potassium-channel
#3
Emre Lacin, Prafulla Aryal, Ian W Glaaser, Karthik Bodhinathan, Eric Tsai, Nidaa Marsh, Stephen J Tucker, Mark S P Sansom, Paul A Slesinger
G protein-gated inwardly rectifying potassium (GIRK) channels control neuronal excitability in the brain and are implicated in several different neurological diseases. The anionic phospholipid phosphatidylinositol 4,5 bisphosphate (PIP2) is an essential cofactor for GIRK channel gating, but the precise mechanism by which PIP2 opens GIRK channels remains poorly understood. Previous structural studies have revealed several highly conserved, positively charged residues in the "tether helix" (C-linker) that interact with the negatively charged PIP2 However, these crystal structures of neuronal GIRK channels in complex with PIP2 provide only snapshots of PIP2's interaction with the channel and thus lack details about the gating transitions triggered by PIP2 binding...
July 18, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28716806/different-strokes-for-different-synaptotagmins
#4
Caitlin Sedwick
JGP study shows how synaptotagmins 1 and 7 affect chromaffin cell granule fusion.
July 17, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28687607/synaptotagmin-isoforms-confer-distinct-activation-kinetics-and-dynamics-to-chromaffin-cell-granules
#5
Tejeshwar C Rao, Zuleirys Santana Rodriguez, Mazdak M Bradberry, Alexandra H Ranski, Peter J Dahl, Michael W Schmidtke, Paul M Jenkins, Daniel Axelrod, Edwin R Chapman, David R Giovannucci, Arun Anantharam
Adrenomedullary chromaffin cells respond to sympathetic nervous system activation by secreting a cocktail of potent neuropeptides and hormones into the circulation. The distinct phases of the chromaffin cell secretory response have been attributed to the progressive fusion of distinct populations of dense core granules with different activation kinetics. However, it has been difficult to define what distinguishes these populations at the molecular level. Functional segregation of granule pools may depend on selective sorting of synaptotagmin-1 (Syt-1) and synaptotagmin-7 (Syt-7), which our previous work showed are rarely cosorted to the same granule...
July 7, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28687606/camp-dependent-regulation-of-iks-single-channel-kinetics
#6
Emely Thompson, Jodene Eldstrom, Maartje Westhoff, Donald McAfee, Elise Balse, David Fedida
The delayed potassium rectifier current, IKs , is composed of KCNQ1 and KCNE1 subunits and plays an important role in cardiac action potential repolarization. During β-adrenergic stimulation, 3'-5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) phosphorylates KCNQ1, producing an increase in IKs current and a shortening of the action potential. Here, using cell-attached macropatches and single-channel recordings, we investigate the microscopic mechanisms underlying the cAMP-dependent increase in IKs current...
July 7, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28630134/correction-clustering-of-ca-2-transients-in-interstitial-cells-of-cajal-defines-slow-wave-duration
#7
Bernard T Drumm, Grant W Hennig, Matthew J Battersby, Erin K Cunningham, Tae Sik Sung, Sean M Ward, Kenton M Sanders, Salah A Baker
No abstract text is available yet for this article.
July 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28626063/no-fuzzy-space-for-intracellular-na-in-healthy-ventricular-myocytes
#8
Frank B Sachse, Robert Clark, Wayne R Giles
No abstract text is available yet for this article.
July 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28619745/many-parts-make-a-whole-calcium-transients-sum-for-slow-waves
#9
Caitlin Sedwick
New JGP study shows how calcium events drive long intestinal slow wave plateaus.
July 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28611079/elevated-camp-improves-signal-to-noise-ratio-in-amphibian-rod-photoreceptors
#10
Luba A Astakhova, Darya A Nikolaeva, Tamara V Fedotkina, Victor I Govardovskii, Michael L Firsov
The absolute sensitivity of vertebrate retinas is set by a background noise, called dark noise, which originates from several different cell types and is generated by different molecular mechanisms. The major share of dark noise is produced by photoreceptors and consists of two components, discrete and continuous. Discrete noise is generated by spontaneous thermal activations of visual pigment. These events are undistinguishable from real single-photon responses (SPRs) and might be considered an equivalent of the signal...
July 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28606910/na-k-pump-inactivation-subsarcolemmal-na-measurements-and-cytoplasmic-ion-turnover-kinetics-contradict-restricted-na-spaces-in-murine-cardiac-myocytes
#11
Fang-Min Lu, Donald W Hilgemann
Decades ago, it was proposed that Na transport in cardiac myocytes is modulated by large changes in cytoplasmic Na concentration within restricted subsarcolemmal spaces. Here, we probe this hypothesis for Na/K pumps by generating constitutive transsarcolemmal Na flux with the Na channel opener veratridine in whole-cell patch-clamp recordings. Using 25 mM Na in the patch pipette, pump currents decay strongly during continuous activation by extracellular K (τ, ∼2 s). In contradiction to depletion hypotheses, the decay becomes stronger when pump currents are decreased by hyperpolarization...
July 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28592421/clustering-of-ca-2-transients-in-interstitial-cells-of-cajal-defines-slow-wave-duration
#12
Bernard T Drumm, Grant W Hennig, Matthew J Battersby, Erin K Cunningham, Tae Sik Sung, Sean M Ward, Kenton M Sanders, Salah A Baker
Interstitial cells of Cajal (ICC) in the myenteric plexus region (ICC-MY) of the small intestine are pacemakers that generate rhythmic depolarizations known as slow waves. Slow waves depend on activation of Ca(2+)-activated Cl(-) channels (ANO1) in ICC, propagate actively within networks of ICC-MY, and conduct to smooth muscle cells where they generate action potentials and phasic contractions. Thus, mechanisms of Ca(2+) regulation in ICC are fundamental to the motor patterns of the bowel. Here, we characterize the nature of Ca(2+) transients in ICC-MY within intact muscles, using mice expressing a genetically encoded Ca(2+) sensor, GCaMP3, in ICC...
July 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28522439/interpreting-the-functional-role-of-a-novel-interaction-motif-in-prokaryotic-sodium-channels
#13
REVIEW
Altin Sula, B A Wallace
Voltage-gated sodium channels enable the translocation of sodium ions across cell membranes and play crucial roles in electrical signaling by initiating the action potential. In humans, mutations in sodium channels give rise to several neurological and cardiovascular diseases, and hence they are targets for pharmaceutical drug developments. Prokaryotic sodium channel crystal structures have provided detailed views of sodium channels, which by homology have suggested potentially important functionally related structural features in human sodium channels...
June 5, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28512088/trpv4-in-the-battle-of-the-sexes
#14
Caitlin Sedwick
New JGP paper explains sexual dimorphism and tissue-specific activity of TRPV4.
June 5, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28507080/divergent-roles-of-a-peripheral-transmembrane-segment-in-ampa-and-nmda-receptors
#15
Johansen B Amin, Catherine L Salussolia, Kelvin Chan, Michael C Regan, Jian Dai, Huan-Xiang Zhou, Hiro Furukawa, Mark E Bowen, Lonnie P Wollmuth
Ionotropic glutamate receptors (iGluRs), including AMPA receptor (AMPAR) and NMDA receptor (NMDAR) subtypes, are ligand-gated ion channels that mediate signaling at the majority of excitatory synapses in the nervous system. The iGluR pore domain is structurally and evolutionarily related to an inverted two-transmembrane K(+) channel. Peripheral to the pore domain in eukaryotic iGluRs is an additional transmembrane helix, the M4 segment, which interacts with the pore domain of a neighboring subunit. In AMPARs, the integrity of the alignment of a specific face of M4 with the adjacent pore domain is essential for receptor oligomerization...
June 5, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28507079/distance-constraints-on-activation-of-trpv4-channels-by-akap150-bound-pkc%C3%AE-in-arterial-myocytes
#16
Sendoa Tajada, Claudia M Moreno, Samantha O'Dwyer, Sean Woods, Daisuke Sato, Manuel F Navedo, L Fernando Santana
TRPV4 (transient receptor potential vanilloid 4) channels are Ca(2+)-permeable channels that play a key role in regulating vascular tone. In arterial myocytes, opening of TRPV4 channels creates local increases in Ca(2+) influx, detectable optically as "TRPV4 sparklets." TRPV4 sparklet activity can be enhanced by the action of the vasoconstrictor angiotensin II (AngII). This modulation depends on the activation of subcellular signaling domains that comprise protein kinase C α (PKCα) bound to the anchoring protein AKAP150...
June 5, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28416648/isoflurane-modulates-activation-and-inactivation-gating-of-the-prokaryotic-na-channel-nachbac
#17
Rheanna M Sand, Kevin J Gingrich, Tamar Macharadze, Karl F Herold, Hugh C Hemmings
Voltage-gated Na(+) channels (Nav) have emerged as important presynaptic targets for volatile anesthetic (VA) effects on synaptic transmission. However, the detailed biophysical mechanisms by which VAs modulate Nav function remain unclear. VAs alter macroscopic activation and inactivation of the prokaryotic Na(+) channel, NaChBac, which provides a useful structural and functional model of mammalian Nav Here, we study the effects of the common general anesthetic isoflurane on NaChBac function by analyzing macroscopic Na(+) currents (INa) in wild-type (WT) channels and mutants with impaired (G229A) or enhanced (G219A) inactivation...
June 5, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28428202/precision-physiology-and-rescue-of-brain-ion-channel-disorders
#18
REVIEW
Jeffrey Noebels
Ion channel genes, originally implicated in inherited excitability disorders of muscle and heart, have captured a major role in the molecular diagnosis of central nervous system disease. Their arrival is heralded by neurologists confounded by a broad phenotypic spectrum of early-onset epilepsy, autism, and cognitive impairment with few effective treatments. As detection of rare structural variants in channel subunit proteins becomes routine, it is apparent that primary sequence alone cannot reliably predict clinical severity or pinpoint a therapeutic solution...
May 1, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28424229/tension-activated-channels-in-the-mechanism-of-osmotic-fitness-in-pseudomonas-aeruginosa
#19
Uğur Çetiner, Ian Rowe, Anthony Schams, Christina Mayhew, Deanna Rubin, Andriy Anishkin, Sergei Sukharev
Pseudomonas aeruginosa (PA) is an opportunistic pathogen with an exceptional ability to adapt to a range of environments. Part of its adaptive potential is the ability to survive drastic osmolarity changes. Upon a sudden dilution of external medium, such as during exposure to rain, bacteria evade mechanical rupture by engaging tension-activated channels that act as osmolyte release valves. In this study, we compare fast osmotic permeability responses in suspensions of wild-type PA and Escherichia coli (EC) strains in stopped-flow experiments and provide electrophysiological descriptions of osmotic-release channels in PA...
May 1, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28424228/pseudomonas-doesn-t-mind-a-dunking
#20
Caitlin Sedwick
A new study explains Pseudomonas aeruginosa's strong resistance to osmotic down-shock.
May 1, 2017: Journal of General Physiology
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