scholarly journals Kinetics of the Addition of Olefins to Si-Centered Radicals: The Critical Role of Dispersion Interactions Revealed by Theory and Experiment

2015 ◽  
Vol 119 (22) ◽  
pp. 5883-5888 ◽  
Author(s):  
Erin R. Johnson ◽  
Owen J. Clarkin ◽  
Stephen G. Dale ◽  
Gino A. DiLabio
2006 ◽  
Vol 281 (43) ◽  
pp. 32649-32659 ◽  
Author(s):  
Zonghe Yan ◽  
Zhaodong Liang ◽  
Tomas Obsil ◽  
Stanko S. Stojilkovic

To study the roles of the Lys313-Ile333 ectodomain sequence of the rat P2X4 receptor in ATP binding and transduction of signals to the channel gate, the conserved Lys313, Tyr315, Gly316, Ike317, Arg318, Asp320, Val323, Lys329, Phe330, and Ile333 residues were mutated. Current recordings were done on lifted cells and ATP was applied using an ultrafast solution-switching system. The rates of wild type channel opening and closing in the presence of ATP, but not the rate of washout-induced closing, were dependent on agonist concentration. All mutants other than I317A were expressed in the plasma membrane at comparable levels. The majority of mutants showed significant changes in the peak amplitude of responses and the EC50 values for ATP. When stimulated with the supramaximal (1.4 mm) ATP concentration, mutants also differed in the kinetics of their activation, deactivation, and/or desensitization. The results suggest a critical role of the Lys313 residue in receptor function other than coordination of the phosphate group of ATP and possible contribution of the Tyr315 residue to the agonist binding module. The pattern of changes of receptor function by mutation of other residues was consistent with the operation of the Gly316-Ile333 sequence as a signal transduction module between the ligand binding domain and the channel gate in the second transmembrane domain.


1955 ◽  
Vol 32 (3) ◽  
pp. 451-467
Author(s):  
H. KACSER

The kinetics of the dark ground cortical change in fertilized sea urchins has been analysed. In normal eggs of Psammechinus miliaris the change appears to obey an autocatalytic mechanism. The evidence from artificial activation suggests that the initiation of the response is caused by a relatively unspecific event. The critical role of calcium is considered in relation to the evidence from eggs fertilized in capillary tubes. This suggests that calcium ions are not concerned with the initiation but with the propagation of the response. The primary change in activation may consist of an increase in permeability at the site of initiation.


2020 ◽  
Vol 167 (7) ◽  
pp. 070538 ◽  
Author(s):  
Montserrat Galceran ◽  
Abdelbast Guerfi ◽  
Michel Armand ◽  
Karim Zaghib ◽  
Montse Casas-Cabanas
Keyword(s):  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anh Tuan Ton ◽  
William Nguyen ◽  
Katrina Sweat ◽  
Yannick Miron ◽  
Eduardo Hernandez ◽  
...  

AbstractLate sodium current (late INa) inhibition has been proposed to suppress the incidence of arrhythmias generated by pathological states or induced by drugs. However, the role of late INa in the human heart is still poorly understood. We therefore investigated the role of this conductance in arrhythmias using adult primary cardiomyocytes and tissues from donor hearts. Potentiation of late INa with ATX-II (anemonia sulcata toxin II) and E-4031 (selective blocker of the hERG channel) slowed the kinetics of action potential repolarization, impaired Ca2+ homeostasis, increased contractility, and increased the manifestation of arrhythmia markers. These effects could be reversed by late INa inhibitors, ranolazine and GS-967. We also report that atrial tissues from donor hearts affected by atrial fibrillation exhibit arrhythmia markers in the absence of drug treatment and inhibition of late INa with GS-967 leads to a significant reduction in arrhythmic behaviour. These findings reveal a critical role for the late INa in cardiac arrhythmias and suggest that inhibition of this conductance could provide an effective therapeutic strategy. Finally, this study highlights the utility of human ex-vivo heart models for advancing cardiac translational sciences.


Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1221
Author(s):  
Matthew H. Doran ◽  
William Lehman

Actin is one of the most abundant and versatile proteins in eukaryotic cells. As discussed in many contributions to this Special Issue, its transition from a monomeric G-actin to a filamentous F-actin form plays a critical role in a variety of cellular processes, including control of cell shape and cell motility. Once polymerized from G-actin, F-actin forms the central core of muscle-thin filaments and acts as molecular tracks for myosin-based motor activity. The ATP-dependent cross-bridge cycle of myosin attachment and detachment drives the sliding of myosin thick filaments past thin filaments in muscle and the translocation of cargo in somatic cells. The variation in actin function is dependent on the variation in muscle and non-muscle myosin isoform behavior as well as interactions with a plethora of additional actin-binding proteins. Extensive work has been devoted to defining the kinetics of actin-based force generation powered by the ATPase activity of myosin. In addition, over the past decade, cryo-electron microscopy has revealed the atomic-evel details of the binding of myosin isoforms on the F-actin surface. Most accounts of the structural interactions between myosin and actin are described from the perspective of the myosin molecule. Here, we discuss myosin-binding to actin as viewed from the actin surface. We then describe conserved structural features of actin required for the binding of all or most myosin isoforms while also noting specific interactions unique to myosin isoforms.


2019 ◽  
Vol 484 ◽  
pp. 933-940 ◽  
Author(s):  
Boeun Lee ◽  
Jihwan Choi ◽  
Subin Na ◽  
Dong-Joo Yoo ◽  
Jong Hak Kim ◽  
...  

2019 ◽  
Vol 7 (28) ◽  
pp. 17008-17013 ◽  
Author(s):  
Tiantian Wang ◽  
Wujie Qiu ◽  
Qi Feng ◽  
Kui Huang ◽  
Xiaolin Zhao ◽  
...  

Electron holes occurring above the O-p Fermi level result in high-barrier kinetics of electrochemical oxygen evolution, which is a major contributor to the wide EW in LLZO.


2001 ◽  
Vol 281 (3) ◽  
pp. C773-C785 ◽  
Author(s):  
James D. Stockand ◽  
Shawn Zeltwanger ◽  
Hui-Fang Bao ◽  
Andrea Becchetti ◽  
Roger T. Worrell ◽  
...  

The A6 cell line was used to study the role of S-adenosyl-l-homocysteine hydrolase (SAHHase) in the aldosterone-induced activation of the epithelial Na+channel (ENaC). Because aldosterone increases methylation of several different molecules, and because this methylation is associated with increased Na+ reabsorption, we tested the hypothesis that aldosterone increases the expression and activity of SAHHase protein. The rationale for this work is that general methylation may be promoted by activation of SAHHase, the only enzyme known to metabolize SAH, a potent end-product inhibitor of methylation. Although aldosterone increased SAHHase activity, steroid did not affect SAHHase expression. Antisense SAHHase oligonucleotide decreased SAHHase expression and activity. Moreover, this oligonucleotide, as well as a pharmacological inhibitor of SAHHase, decreased aldosterone-induced activity of ENaC via a decrease in ENaC open probability. The kinetics of ENaC in cells treated with antisense plus aldosterone were similar to those reported previously for the channel in the absence of steroid. This is the first report showing that active SAHHase, in part, increases ENaC open probability by reducing the transition rate from open states in response to aldosterone. Thus aldosterone-induced SAHHase activity plays a critical role in shifting ENaC from a gating mode with short open and closed times to one with longer open and closed times.


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