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Journal of General Physiology

Eduardo Ríos
Ryanodine-sensitive intracellular Ca2+ channels (RyRs) open upon binding Ca2+ at cytosolic-facing sites. This results in concerted, self-reinforcing opening of RyRs clustered in specialized regions on the membranes of Ca2+ storage organelles (endoplasmic reticulum and sarcoplasmic reticulum), a process that produces Ca2+ -induced Ca2+ release (CICR). The process is optimized to achieve large but brief and localized increases in cytosolic Ca2+ concentration, a feature now believed to be critical for encoding the multiplicity of signals conveyed by this ion...
March 7, 2018: Journal of General Physiology
Philip D Kiser, Jianye Zhang, Aditya Sharma, Juan M Angueyra, Alexander V Kolesnikov, Mohsen Badiee, Gregory P Tochtrop, Junzo Kinoshita, Neal S Peachey, Wei Li, Vladimir J Kefalov, Krzysztof Palczewski
Visual function in vertebrates critically depends on the continuous regeneration of visual pigments in rod and cone photoreceptors. RPE65 is a well-established retinoid isomerase in the pigment epithelium that regenerates rhodopsin during the rod visual cycle; however, its contribution to the regeneration of cone pigments remains obscure. In this study, we use potent and selective RPE65 inhibitors in rod- and cone-dominant animal models to discern the role of this enzyme in cone-mediated vision. We confirm that retinylamine and emixustat-family compounds selectively inhibit RPE65 over DES1, the putative retinoid isomerase of the intraretinal visual cycle...
March 2, 2018: Journal of General Physiology
Laura-Marie Winterstein, Kerri Kukovetz, Oliver Rauh, Daniel L Turman, Christian Braun, Anna Moroni, Indra Schroeder, Gerhard Thiel
Recent studies have shown that membrane proteins can be efficiently synthesized in vitro before spontaneously inserting into soluble nanoscale lipid bilayers called nanodiscs (NDs). In this paper, we present experimental details that allow a combination of in vitro translation of ion channels into commercially available NDs followed by their direct reconstitution from these nanobilayers into standard bilayer setups for electrophysiological characterization. We present data showing that two model K+ channels, Kcv and KcsA, as well as a recently discovered dual-topology F- channel, Fluc, can be reliably reconstituted from different types of NDs into bilayers without contamination from the in vitro translation cocktail...
February 27, 2018: Journal of General Physiology
I Scott Ramsey, John A DeSimone
No abstract text is available yet for this article.
February 26, 2018: Journal of General Physiology
Sharona E Gordon
No abstract text is available yet for this article.
February 22, 2018: Journal of General Physiology
Mohamed Chahine
CaV 1.1 channels are organized into four homologous domains (domains I-IV), each composed of a nonpermeable voltage sensor domain (VSD) and a calcium-permeable pore domain. Mutations in the VSD may create a leak and render the VSD permeable to ions. Recording of such a leak current, known as a gating pore current, was hampered by the low expression of these channels in a heterologous expression system. In this issue, Wu et al. (2018. J. Gen. Physiol. show for the first time the biophysical properties of this current using Stac3 to boost the expression of the CaV 1...
February 21, 2018: Journal of General Physiology
Edward N Pugh
Vertebrate rod photoreceptors evolved the astonishing ability to respond reliably to single photons. In parallel, the proximate neurons of the visual system evolved the ability to reliably encode information from a few single-photon responses (SPRs) as arising from the presence of an object of interest in the visual environment. These amazing capabilities were first inferred from measurements of human visual threshold by Hecht et al. (1942), whose paper has since been cited over 1,000 times. Subsequent research, in part inspired by Hecht et al...
February 21, 2018: Journal of General Physiology
Alexander Polster, Benjamin R Nelson, Symeon Papadopoulos, Eric N Olson, Kurt G Beam
In skeletal muscle, residues 720-764/5 within the CaV 1.1 II-III loop form a critical domain that plays an essential role in transmitting the excitation-contraction (EC) coupling Ca2+ release signal to the type 1 ryanodine receptor (RyR1) in the sarcoplasmic reticulum. However, the identities of proteins that interact with the loop and its critical domain and the mechanism by which the II-III loop regulates RyR1 gating remain unknown. Recent work has shown that EC coupling in skeletal muscle of fish and mice depends on the presence of Stac3, an adaptor protein that is highly expressed only in skeletal muscle...
February 21, 2018: Journal of General Physiology
Caitlin Sedwick
JGP study explores a novel photoreception pathway in a marine mollusk.
February 20, 2018: Journal of General Physiology
Felix Neumaier, Serdar Alpdogan, Jürgen Hescheler, Toni Schneider
R-type currents mediated by native and recombinant Ca v 2.3 voltage-gated Ca 2+ channels (VGCCs) exhibit facilitation (run-up) and subsequent decline (run-down) in whole-cell patch-clamp recordings. A better understanding of the two processes could provide insight into constitutive modulation of the channels in intact cells, but low expression levels and the need for pharmacological isolation have prevented investigations in native systems. Here, to circumvent these limitations, we use conventional and perforated-patch-clamp recordings in a recombinant expression system, which allows us to study the effects of cell dialysis in a reproducible manner...
February 16, 2018: Journal of General Physiology
Peter S Hasenhuetl, Shreyas Bhat, Felix P Mayer, Harald H Sitte, Michael Freissmuth, Walter Sandtner
The plasmalemmal monoamine transporters for dopamine, norepinephrine, and serotonin (SERT) are targets for amphetamines. In vivo, amphetamines elicit most, if not all, of their actions by triggering monoamine efflux. This is thought to be accomplished by an amphetamine-induced switch from the forward-transport to the substrate-exchange mode. The mechanism underlying this switch has remained elusive; available kinetic models posit that substrates and cosubstrate Na+ ions bind either in a random or in a sequential order...
February 9, 2018: Journal of General Physiology
Estefania Barreto-Ojeda, Valentina Corradi, Ruo-Xu Gu, D Peter Tieleman
P-glycoprotein (P-gp) exports a broad range of dissimilar compounds, including drugs, lipids, and lipid-like molecules. Because of its substrate promiscuity, P-gp is a key player in the development of cancer multidrug resistance. Although P-gp is one of the most studied ABC transporters, the mechanism by which its substrates access the cavity remains unclear. In this study, we perform coarse-grained molecular dynamics simulations to explore possible lipid access pathways in the inward-facing conformation of P-gp embedded in bilayers of different lipid compositions...
February 6, 2018: Journal of General Physiology
Fenfen Wu, Marbella Quinonez, Marino DiFranco, Stephen C Cannon
Mutations of CaV1.1, the pore-forming subunit of the L-type Ca2+ channel in skeletal muscle, are an established cause of hypokalemic periodic paralysis (HypoPP). However, functional assessment of HypoPP mutant channels has been hampered by difficulties in achieving sufficient plasma membrane expression in cells that are not of muscle origin. In this study, we show that coexpression of Stac3 dramatically increases the expression of human CaV1.1 (plus α2-δ1b and β1a subunits) at the plasma membrane of Xenopus laevis oocytes...
January 31, 2018: Journal of General Physiology
Philip Kiær Ahring, Vivian Wan Yu Liao, Thomas Balle
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are vital for normal mammalian brain function. Cys-loop receptors are pentameric ligand-gated ion channels formed from five identical or homologous subunits oriented around a central ion-conducting pore, which result in homomeric or heteromeric receptors, respectively. Within a given Cys-loop receptor family, many different heteromeric receptors can assemble from a common set of subunits, and understanding the properties of these heteromeric receptors is crucial for the continuing quest to generate novel treatments for human diseases...
January 30, 2018: Journal of General Physiology
Oscar Arenas, Tomás Osorno, Gerardo Malagón, Camila Pulido, María Del Pilar Gomez, Enrico Nasi
The two basic animal photoreceptor types, ciliary and microvillar, use different light-transduction schemes: their photopigments couple to Gt versus Gq proteins, respectively, to either mobilize cyclic nucleotides or trigger a lipid signaling cascade. A third class of photoreceptors has been described in the dual retina of some marine invertebrates; these present a ciliary morphology but operate via radically divergent mechanisms, prompting the suggestion that they comprise a novel lineage of light sensors...
January 26, 2018: Journal of General Physiology
Sharona E Gordon
No abstract text is available yet for this article.
January 24, 2018: Journal of General Physiology
Bertil Hille
This essay begins with a description of the founding years of Journal of General Physiology (JGP) and a historical overview of the content of the journal. It then turns to key conceptual articles published in JGP that advanced the field of membrane permeation and ion selectivity. Much of this information comes from reading the online archives of JGP and searches in PubMed.
January 23, 2018: Journal of General Physiology
Richard W Aldrich
No abstract text is available yet for this article.
January 23, 2018: Journal of General Physiology
Clara Franzini-Armstrong
No abstract text is available yet for this article.
January 22, 2018: Journal of General Physiology
Ruth D Murrell-Lagnado
No abstract text is available yet for this article.
January 22, 2018: Journal of General Physiology
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