scholarly journals Open‐channel blocking action of volatile anaesthetics desflurane and sevoflurane on human voltage‐gated K v 1.5 channel

2020 ◽  
Vol 177 (16) ◽  
pp. 3811-3827
Author(s):  
Yutaka Fukushima ◽  
Akiko Kojima ◽  
Xinya Mi ◽  
Wei‐Guang Ding ◽  
Hirotoshi Kitagawa ◽  
...  
Keyword(s):  
Open Channel ◽  
Volatile Anaesthetics ◽  
Voltage Gated ◽  
Channel Blocking

scholarly journals Interactions among DIV voltage-sensor movement, fast inactivation, and resurgent Na current induced by the NaVβ4 open-channel blocking peptide

2013 ◽  
Vol 142 (3) ◽  
pp. 191-206 ◽  
Author(s):  
Amanda H. Lewis ◽  
Indira M. Raman
Keyword(s):  
Open Channel ◽  
Voltage Sensor ◽  
Channel Block ◽  
Na Channels ◽  
Fast Inactivation ◽  
Na Current ◽  
Open Channel Block ◽  
Channel Blocking ◽  
Open States ◽  
Resurgent Currents

Resurgent Na current flows as voltage-gated Na channels recover through open states from block by an endogenous open-channel blocking protein, such as the NaVβ4 subunit. The open-channel blocker and fast-inactivation gate apparently compete directly, as slowing the onset of fast inactivation increases resurgent currents by favoring binding of the blocker. Here, we tested whether open-channel block is also sensitive to deployment of the DIV voltage sensor, which facilitates fast inactivation. We expressed NaV1.4 channels in HEK293t cells and assessed block by a free peptide replicating the cytoplasmic tail of NaVβ4 (the “β4 peptide”). Macroscopic fast inactivation was disrupted by mutations of DIS6 (L443C/A444W; “CW” channels), which reduce fast-inactivation gate binding, and/or by the site-3 toxin ATX-II, which interferes with DIV movement. In wild-type channels, the β4 peptide competed poorly with fast inactivation, but block was enhanced by ATX. With the CW mutation, large peptide-induced resurgent currents were present even without ATX, consistent with increased open-channel block upon depolarization and slower deactivation after blocker unbinding upon repolarization. The addition of ATX greatly increased transient current amplitudes and further enlarged resurgent currents, suggesting that pore access by the blocker is actually decreased by full deployment of the DIV voltage sensor. ATX accelerated recovery from block at hyperpolarized potentials, however, suggesting that the peptide unbinds more readily when DIV voltage-sensor deployment is disrupted. These results are consistent with two open states in Na channels, dependent on the DIV voltage-sensor position, which differ in affinity for the blocking protein.

GABAA receptor activation and open-channel block by volatile anaesthetics: a new principle of receptor modulation?

2002 ◽  
Vol 451 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Rainer Haseneder ◽  
Gerhard Rammes ◽  
Walter Zieglgänsberger ◽  
Eberhard Kochs ◽  
Gerhard Hapfelmeier
Keyword(s):  
Gabaa Receptor ◽  
Open Channel ◽  
Receptor Activation ◽  
Channel Block ◽  
Volatile Anaesthetics ◽  
Open Channel Block ◽  
Receptor Modulation

scholarly journals Discovery of Lacosamide Affinity Bait Agents That Exhibit Potent Voltage-Gated Sodium Channel Blocking Properties

2013 ◽  
Vol 4 (3) ◽  
pp. 463-474 ◽  
Author(s):  
Ki Duk Park ◽  
Xiao-Fang Yang ◽  
Hyosung Lee ◽  
Erik T. Dustrude ◽  
Yuying Wang ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Blocking

scholarly journals Hexacyclododecylamines with Sigma-1 Receptor Affinity and Calcium Channel Modulating Ability

2019 ◽  
Vol 13 (1) ◽  
pp. 29-39 ◽  
Author(s):  
Jacques Joubert ◽  
Natasha Strydom ◽  
Werner J. Geldenhuys ◽  
Yolande Greyling ◽  
Sandra V. Dyk ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Drug Target ◽  
Potential Effect ◽  
Sigma 1 Receptor ◽  
Voltage Gated ◽  
Brain Barrier Permeability ◽  
Channel Blocking ◽  
Sigma 1 ◽  
Voltage Gated Calcium Channel ◽  
Privileged Structures

Introduction: Recent research points to the Sigma Receptor (σR) as a possible neuromodulatory system with multi-functional action and σ1Rs have been suggested as a drug target for a number of CNS conditions. Hexacyclododecylamines have shown σ1R activity and provide an advantageous scaffold for drug design that can improve the blood-brain barrier permeability of privileged structures. Methods and Materials: A series of oxa- and aza- hexaxcyclododecylamines were synthesised and evaluated for sigma-1 receptor activity and voltage-gated calcium channel blocking ability to determine the effect of inclusion of amine containing heterocycles. Results & Discussion: The compounds had promising σ1R activities (Ki = 0.067 – 11.86 µM) with the aza-hexacyclododecylamines 12, 24 and 27 showing some of the highest affinities (Ki = 0.067 µM, 0.215 µM and 0.496 µM respectively). This confirms, as observed in previous studies, that the aza compounds are more favourable for σ1R binding than their oxa counterparts. The addition of the amine heterocycle showed affinities similar to that of related structures with only two lipophilic binding regions. This indicates that the inclusion of an amine heterocycle into these structures is a viable option in the design of new σ1R ligands. Significant voltage-gated calcium channel blocking ability was also observed for 12, 24 and 27, suggesting a link between σ1R activity and intracellular calcium levels. Conclusion: The σ1R activity and potential effect on other receptor classes and calcium channels could prove beneficial in pharmacological application.

scholarly journals Current statins show calcium channel blocking activity through voltage gated channels

2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Niaz Ali ◽  
Robina Begum ◽  
Muhammad Saleh Faisal ◽  
Aslam Khan ◽  
Muhammad Nabi ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Voltage Gated ◽  
Channel Blocking ◽  
Blocking Activity ◽  
Voltage Gated Channels

Synthesis and Evaluation of Voltage‐Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

ChemMedChem ◽  
2020 ◽  
Author(s):  
Alessia Carocci ◽  
Mariagrazia Roselli ◽  
Roberta Budriesi ◽  
Matteo Micucci ◽  
Jean‐François Desaphy ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Antioxidant Activities ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Blocking

The open channel blocking drug, IEM-1460, reveals functionally distinct α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors in rat brain neurons

Neuroscience ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 261-268 ◽  
Author(s):  
M.V Samoilova ◽  
S.L Buldakova ◽  
V.S Vorobjev ◽  
I.N Sharonova ◽  
L.G Magazanik
Keyword(s):  
Rat Brain ◽  
Open Channel ◽  
Blocking Drug ◽  
Brain Neurons ◽  
Channel Blocking ◽  
Rat Brain Neurons
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