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Journal of General Physiology

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https://www.readbyqxmd.com/read/28522439/interpreting-the-functional-role-of-a-novel-interaction-motif-in-prokaryotic-sodium-channels
#1
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...
May 18, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28512088/trpv4-in-the-battle-of-the-sexes
#2
Caitlin Sedwick
New JGP paper explains sexual dimorphism and tissue-specific activity of TRPV4.
May 16, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28507080/divergent-roles-of-a-peripheral-transmembrane-segment-in-ampa-and-nmda-receptors
#3
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...
May 15, 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
#4
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...
May 15, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28416648/isoflurane-modulates-activation-and-inactivation-gating-of-the-prokaryotic-na-channel-nachbac
#5
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...
April 17, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28428202/precision-physiology-and-rescue-of-brain-ion-channel-disorders
#6
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
#7
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
#8
Caitlin Sedwick
A new study explains Pseudomonas aeruginosa's strong resistance to osmotic down-shock.
May 1, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28416647/identifiability-reducibility-and-adaptability-in-allosteric-macromolecules
#9
Gergő Bohner, Gaurav Venkataraman
The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed "allostery," is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca(2+)-activated K(+) (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay...
May 1, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28389584/control-of-kir-channel-gating-by-cytoplasmic-domain-interface-interactions
#10
William F Borschel, Shizhen Wang, Sunjoo Lee, Colin G Nichols
Inward rectifier potassium (Kir) channels are expressed in almost all mammalian tissues and play critical roles in the control of excitability. Pancreatic ATP-sensitive K (KATP) channels are key regulators of insulin secretion and comprise Kir6.2 subunits coupled to sulfonylurea receptors. Because these channels are reversibly inhibited by cytoplasmic ATP, they link cellular metabolism with membrane excitability. Loss-of-function mutations in the pore-forming Kir6.2 subunit cause congenital hyperinsulinism as a result of diminished channel activity...
May 1, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28360219/a-new-mechanism-of-voltage-dependent-gating-exposed-by-kv10-1-channels-interrupted-between-voltage-sensor-and-pore
#11
Adam P Tomczak, Jorge Fernández-Trillo, Shashank Bharill, Ferenc Papp, Gyorgy Panyi, Walter Stühmer, Ehud Y Isacoff, Luis A Pardo
Voltage-gated ion channels couple transmembrane potential changes to ion flow. Conformational changes in the voltage-sensing domain (VSD) of the channel are thought to be transmitted to the pore domain (PD) through an α-helical linker between them (S4-S5 linker). However, our recent work on channels disrupted in the S4-S5 linker has challenged this interpretation for the KCNH family. Furthermore, a recent single-particle cryo-electron microscopy structure of KV10.1 revealed that the S4-S5 linker is a short loop in this KCNH family member, confirming the need for an alternative gating model...
May 1, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28330839/evolutionary-insights-into-t-type-ca-2-channel-structure-function-and-ion-selectivity-from-the-trichoplax-adhaerens-homologue
#12
Carolyn L Smith, Salsabil Abdallah, Yuen Yan Wong, Phuong Le, Alicia N Harracksingh, Liana Artinian, Arianna N Tamvacakis, Vincent Rehder, Thomas S Reese, Adriano Senatore
Four-domain voltage-gated Ca(2+) (Cav) channels play fundamental roles in the nervous system, but little is known about when or how their unique properties and cellular roles evolved. Of the three types of metazoan Cav channels, Cav1 (L-type), Cav2 (P/Q-, N- and R-type) and Cav3 (T-type), Cav3 channels are optimized for regulating cellular excitability because of their fast kinetics and low activation voltages. These same properties permit Cav3 channels to drive low-threshold exocytosis in select neurons and neurosecretory cells...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28302678/bright-flash-response-recovery-of-mammalian-rods-in-vivo-is-rate-limited-by-rgs9
#13
Gabriel Peinado Allina, Christopher Fortenbach, Franklin Naarendorp, Owen P Gross, Edward N Pugh, Marie E Burns
The temporal resolution of scotopic vision is thought to be constrained by the signaling kinetics of retinal rods, which use a highly amplified G-protein cascade to transduce absorbed photons into changes in membrane potential. Much is known about the biochemical mechanisms that determine the kinetics of rod responses ex vivo, but the rate-limiting mechanisms in vivo are unknown. Using paired flash electroretinograms with improved signal-to-noise, we have recorded the amplitude and kinetics of rod responses to a wide range of flash strengths from living mice...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28298356/the-glass-micropipette-electrode-a-history-of-its-inventors-and-users-to-1950
#14
Allan H Bretag
Soon after the glass micropipette was invented as a micro-tool for manipulation of single bacteria and the microinjection and microsurgery of living cells, it was seen to hold promise as a microelectrode to stimulate individual cells electrically and to study electrical potentials in them. Initial successes and accurate mechanistic explanations of the results were achieved in giant plant cells in the 1920s. Long known surface electrical activity in nerves and muscles was only resolved at a similar cellular level in the 1930s and 1940s after the discovery of giant nerve fibers and the development of finer tipped microelectrodes for normal-sized cells...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28289068/sodium-ion-unlocks-understanding-of-channel-blockade
#15
Caitlin Sedwick
New simulations explain how several types of drugs block sodium channels.
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28283577/distinct-roles-of-light-activated-channels-trp-and-trpl-in-photoreceptors-of-periplaneta-americana
#16
Paulus Saari, Andrew S French, Päivi H Torkkeli, Hongxia Liu, Esa-Ville Immonen, Roman V Frolov
Electrophysiological studies in Drosophila melanogaster and Periplaneta americana have found that the receptor current in their microvillar photoreceptors is generated by two light-activated cationic channels, TRP (transient receptor potential) and TRPL (TRP-like), each having distinct properties. However, the relative contribution of the two channel types to sensory information coding by photoreceptors remains unclear. We recently showed that, in contrast to the diurnal Drosophila in which TRP is the principal phototransduction channel, photoreceptors of the nocturnal P...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28270405/protein-ligands-for-studying-ion-channel-proteins
#17
Tanmay Chavan, Merritt Maduke, Kenton Swartz
No abstract text is available yet for this article.
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28264886/cftr-gating-invisible-transitions-made-visible
#18
László Csanády
No abstract text is available yet for this article.
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28258204/mechanism-of-sodium-channel-block-by-local-anesthetics-antiarrhythmics-and-anticonvulsants
#19
Denis B Tikhonov, Boris S Zhorov
Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28258203/mechanism-of-single-and-double-sided-inhibition-of-dual-topology-fluoride-channels-by-synthetic-monobodies
#20
Daniel L Turman, Randy B Stockbridge
The Fluc family of proteins comprises small, electrodiffusive fluoride channels, which prevent accumulation of toxic F(-) ions in microorganisms. Recent crystal structures have confirmed their unusual architecture, in which a pair of antiparallel subunits convenes to form a dimer with a twofold symmetry axis parallel to the plane of the membrane. These structures have also revealed the interactions between Fluc channels and several different fibronectin domain monobodies that inhibit Fluc-mediated F(-) currents; in all structures, each channel binds to two monobodies symmetrically, one on either side of the membrane...
April 3, 2017: Journal of General Physiology
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