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Journal of General Physiology

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https://www.readbyqxmd.com/read/28428202/precision-physiology-and-rescue-of-brain-ion-channel-disorders
#1
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...
April 20, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28424229/tension-activated-channels-in-the-mechanism-of-osmotic-fitness-in-pseudomonas-aeruginosa
#2
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...
April 19, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28424228/pseudomonas-doesn-t-mind-a-dunking
#3
Caitlin Sedwick
A new study explains Pseudomonas aeruginosa's strong resistance to osmotic down-shock.
April 19, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28416648/isoflurane-modulates-activation-and-inactivation-gating-of-the-prokaryotic-na-channel-nachbac
#4
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/28416647/identifiability-reducibility-and-adaptability-in-allosteric-macromolecules
#5
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...
April 17, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28389584/control-of-kir-channel-gating-by-cytoplasmic-domain-interface-interactions
#6
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...
April 7, 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
#7
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...
March 30, 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/28246117/probing-the-conformation-of-a-conserved-glutamic-acid-within-the-cl-pathway-of-a-clc-h-cl-exchanger
#17
Malvin Vien, Daniel Basilio, Lilia Leisle, Alessio Accardi
The CLC proteins form a broad family of anion-selective transport proteins that includes both channels and exchangers. Despite extensive structural, functional, and computational studies, the transport mechanism of the CLC exchangers remains poorly understood. Several transport models have been proposed but have failed to capture all the key features of these transporters. Multiple CLC crystal structures have suggested that a conserved glutamic acid, Gluex, can adopt three conformations and that the interconversion of its side chain between these states underlies H(+)/Cl(-) exchange...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28246116/understanding-the-conformational-motions-of-rck-gating-rings
#18
REVIEW
Teresa Giraldez, Brad S Rothberg
Regulator of conduction of K(+) (RCK) domains are ubiquitous regulators of channel and transporter activity in prokaryotes and eukaryotes. In humans, RCK domains form an integral component of large-conductance calcium-activated K channels (BK channels), key modulators of nerve, muscle, and endocrine cell function. In this review, we explore how the study of RCK domains in bacterial and human channels has contributed to our understanding of the structural basis of channel function. This knowledge will be critical in identifying mechanisms that underlie BK channelopathies that lead to epilepsy and other diseases, as well as regions of the channel that might be successfully targeted to treat such diseases...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28242630/electrostatic-tuning-of-the-pre-and-post-hydrolytic-open-states-in-cftr
#19
Jingyao Zhang, Tzyh-Chang Hwang
Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that couples adenosine triphosphate (ATP) hydrolysis at its nucleotide-binding domains to gating transitions in its transmembrane domains. We previously reported that the charge-neutralized mutant R352C shows two distinct open states, O1 and O2 The two states could be distinguished by their single-channel current amplitudes: O1 having a smaller amplitude (representing a prehydrolytic open state) and O2 having a larger amplitude (representing a post-hydrolytic open state)...
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28232510/regulation-of-na-channel-inactivation-by-the-diii-and-div-voltage-sensing-domains
#20
Eric J Hsu, Wandi Zhu, Angela R Schubert, Taylor Voelker, Zoltan Varga, Jonathan R Silva
Functional eukaryotic voltage-gated Na(+) (NaV) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical NaV channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair NaV channel inactivation...
March 6, 2017: Journal of General Physiology
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