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Journal of General Physiology

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https://www.readbyqxmd.com/read/28330839/evolutionary-insights-into-t-type-ca-2-channel-structure-function-and-ion-selectivity-from-the-trichoplax-adhaerens-homologue
#1
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...
March 22, 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
#2
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...
March 16, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28298356/the-glass-micropipette-electrode-a-history-of-its-inventors-and-users-to-1950
#3
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...
March 15, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28289068/sodium-ion-unlocks-understanding-of-channel-blockade
#4
Caitlin Sedwick
New simulations explain how several types of drugs block sodium channels.
March 13, 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
#5
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...
March 10, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28270405/protein-ligands-for-studying-ion-channel-proteins
#6
Tanmay Chavan, Merritt Maduke, Kenton Swartz
No abstract text is available yet for this article.
March 7, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28264886/cftr-gating-invisible-transitions-made-visible
#7
László Csanády
No abstract text is available yet for this article.
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28258204/mechanism-of-sodium-channel-block-by-local-anesthetics-antiarrhythmics-and-anticonvulsants
#8
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...
March 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
#9
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...
March 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
#10
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...
February 28, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28246116/understanding-the-conformational-motions-of-rck-gating-rings
#11
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...
February 28, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28242630/electrostatic-tuning-of-the-pre-and-post-hydrolytic-open-states-in-cftr
#12
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
#13
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
https://www.readbyqxmd.com/read/28213459/acting-on-an-impulse-or-two-advantages-of-high-frequency-tetanic-onset-in-skeletal-muscle
#14
Richard L Moss, Thomas L Lynch, Daniel P Fitzsimons
No abstract text is available yet for this article.
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28209802/doublet-stimulation-increases-ca-2-binding-to-troponin-c-to-ensure-rapid-force-development-in-skeletal-muscle
#15
Anthony J Bakker, Tanya R Cully, Catherine D Wingate, Christopher J Barclay, Bradley S Launikonis
Fast-twitch skeletal muscle fibers are often exposed to motor neuron double discharges (≥200 Hz), which markedly increase both the rate of contraction and the magnitude of the resulting force responses. However, the mechanism responsible for these effects is poorly understood, likely because of technical limitations in previous studies. In this study, we measured cytosolic Ca(2+) during doublet activation using the low-affinity indicator Mag-Fluo-4 at high temporal resolution and modeled the effects of doublet stimulation on sarcoplasmic reticulum (SR) Ca(2+) release, binding of Ca(2+) to cytosolic buffers, and force enhancement in fast-twitch fibers...
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28202492/gating-ring-strengthens-marriage-of-bk-channel-voltage-sensing-to-pore-opening
#16
Caitlin Sedwick
A new JGP study shows that the gating ring helps the voltage-sensing domain open the BK channel's pore.
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28196879/deletion-of-cytosolic-gating-ring-decreases-gate-and-voltage-sensor-coupling-in-bk-channels
#17
Guohui Zhang, Yanyan Geng, Yakang Jin, Jingyi Shi, Kelli McFarland, Karl L Magleby, Lawrence Salkoff, Jianmin Cui
Large conductance Ca(2+)-activated K(+) channels (BK channels) gate open in response to both membrane voltage and intracellular Ca(2+) The channel is formed by a central pore-gate domain (PGD), which spans the membrane, plus transmembrane voltage sensors and a cytoplasmic gating ring that acts as a Ca(2+) sensor. How these voltage and Ca(2+) sensors influence the common activation gate, and interact with each other, is unclear. A previous study showed that a BK channel core lacking the entire cytoplasmic gating ring (Core-MT) was devoid of Ca(2+) activation but retained voltage sensitivity (Budelli et al...
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28167663/fusion-pores-and-their-control-of-neurotransmitter-and-hormone-release
#18
REVIEW
Che-Wei Chang, Chung-Wei Chiang, Meyer B Jackson
Ca(2+)-triggered exocytosis functions broadly in the secretion of chemical signals, enabling neurons to release neurotransmitters and endocrine cells to release hormones. The biological demands on this process can vary enormously. Although synapses often release neurotransmitter in a small fraction of a millisecond, hormone release can be orders of magnitude slower. Vesicles usually contain multiple signaling molecules that can be released selectively and conditionally. Cells are able to control the speed, concentration profile, and content selectivity of release by tuning and tailoring exocytosis to meet different biological demands...
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28153865/mechanisms-creating-transient-and-sustained-photoresponses-in-mammalian-retinal-ganglion-cells
#19
Xiwu Zhao, Aaron N Reifler, Melanie M Schroeder, Elizabeth R Jaeckel, Andrew P Chervenak, Kwoon Y Wong
Retinal neurons use sustained and transient light responses to encode visual stimuli of different frequency ranges, but the underlying mechanisms remain poorly understood. In particular, although earlier studies in retinal ganglion cells (RGCs) proposed seven potential mechanisms, all seven have since been disputed, and it remains unknown whether different RGC types use different mechanisms or how many mechanisms are used by each type. Here, we conduct a comprehensive survey in mice and rats of 12 candidate mechanisms that could conceivably produce tonic rod/cone-driven ON responses in intrinsically photosensitive RGCs (ipRGCs) and transient ON responses in three types of direction-selective RGCs (TRHR+, Hoxd10+ ON, and Hoxd10+ ON-OFF cells)...
March 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28153864/the-state-of-the-community-jgp-in-2017
#20
EDITORIAL
Sharona E Gordon
Amid a difficult year for science and scientists, The Journal of General Physiology is thriving and gearing up for its 100th anniversary celebrations.
February 2017: Journal of General Physiology
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