Open-channel-block induced by the neurotransmitter glycine in homomeric alpha1-GlyR and heteromeric alpha1/beta1- GlyR

2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
Y.P Song ◽  
F Schlesinger ◽  
S Petri ◽  
R Dengler ◽  
K Krampfl
Keyword(s):  
Open Channel ◽  
Channel Block ◽  
Open Channel Block

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 Membrane Lipid Modulations Remove Divalent Open Channel Block from TRP-Like and NMDA Channels

2009 ◽  
Vol 29 (8) ◽  
pp. 2371-2383 ◽  
Author(s):  
M. Parnas ◽  
B. Katz ◽  
S. Lev ◽  
V. Tzarfaty ◽  
D. Dadon ◽  
...  
Keyword(s):  
Open Channel ◽  
Membrane Lipid ◽  
Channel Block ◽  
Open Channel Block ◽  
Nmda Channels

Open channel block of human heart hKv1.5 by the beta-subunit hKv beta 1.2

1997 ◽  
Vol 272 (6) ◽  
pp. H2932-H2941 ◽  
Author(s):  
M. De Biasi ◽  
Z. Wang ◽  
E. Accili ◽  
B. Wible ◽  
D. Fedida
Keyword(s):  
Human Heart ◽  
Open Channel ◽  
Beta Subunit ◽  
Beta Subunits ◽  
Channel Block ◽  
Open Channel Block ◽  
Pharmacological Characterization ◽  
Kinetics Of ◽  
K Currents

Voltage-gated K+ currents in human heart are likely to derive from multisubunit complexes of pore-forming alpha-subunits with one or more auxiliary beta-subunits. We recently cloned a novel beta-subunit from human atrium, hKv beta 1.2 (K. Majumder, M. De Biasi, Z. Wang, and B. A. Wible. FEBS Lett. 361: 13-16, 1995), and showed that it interacts with channels in the Kv1 family. Here we characterize the interaction of hKv beta 1.2 with hKv1.5 in terms of a two-closed-state and one-open-state open channel block model. After coexpression in Xenopus oocytes, hKv1.5 currents were reduced in the presence of hKv beta 1.2, and at positive potentials an inactivation process was introduced. Deactivation kinetics of hKv1.5 were slowed, and there was an increased steepness with a -14-mV hyperpolarizing shift in the midpoint of steady-state activation. The model was able to predict all the above features of the interaction of hKv1.5 and hKv beta 1.2 as a result of rapid open channel block of activated channels. Understanding the mechanism of hKv beta 1.2 action on heart K+ channels will further aid the development of the functional and pharmacological characterization of native cardiac K+ currents.

Molecular Basis for a High-Potency Open-Channel Block of Kv1.5 Channel by the Endocannabinoid Anandamide

2010 ◽  
Vol 77 (5) ◽  
pp. 751-758 ◽  
Author(s):  
Eloy G. Moreno-Galindo ◽  
Gabriel F. Barrio-Echavarría ◽  
José C. Vásquez ◽  
Niels Decher ◽  
Frank B. Sachse ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Open Channel ◽  
Channel Block ◽  
High Potency ◽  
Open Channel Block

scholarly journals Open Channel Block by Ca2+ Underlies the Voltage Dependence of Drosophila TRPL Channel

2006 ◽  
Vol 129 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Moshe Parnas ◽  
Ben Katz ◽  
Baruch Minke
Keyword(s):  
Open Channel ◽  
Transient Receptor Potential ◽  
Voltage Dependence ◽  
Trp Channels ◽  
Divalent Cations ◽  
Dependent Manner ◽  
Channel Block ◽  
Open Channel Block ◽  
Gating Mechanism ◽  
Voltage Dependent

The light-activated channels of Drosophila photoreceptors transient receptor potential (TRP) and TRP-like (TRPL) show voltage-dependent conductance during illumination. Recent studies implied that mammalian members of the TRP family, which belong to the TRPV and TRPM subfamilies, are intrinsically voltage-gated channels. However, it is unclear whether the Drosophila TRPs, which belong to the TRPC subfamily, share the same voltage-dependent gating mechanism. Exploring the voltage dependence of Drosophila TRPL expressed in S2 cells, we found that the voltage dependence of this channel is not an intrinsic property since it became linear upon removal of divalent cations. We further found that Ca2+ blocked TRPL in a voltage-dependent manner by an open channel block mechanism, which determines the frequency of channel openings and constitutes the sole parameter that underlies its voltage dependence. Whole cell recordings from a Drosophila mutant expressing only TRPL indicated that Ca2+ block also accounts for the voltage dependence of the native TRPL channels. The open channel block by Ca2+ that we characterized is a useful mechanism to improve the signal to noise ratio of the response to intense light when virtually all the large conductance TRPL channels are blocked and only the low conductance TRP channels with lower Ca2+ affinity are active.

scholarly journals Y3+ Block Demonstrates an Intracellular Activation Gate for the α1G T-type Ca2+ Channel

2004 ◽  
Vol 124 (6) ◽  
pp. 631-640 ◽  
Author(s):  
Carlos A. Obejero-Paz ◽  
I. Patrick Gray ◽  
Stephen W. Jones
Keyword(s):  
Open Channel ◽  
Voltage Dependence ◽  
Channel Block ◽  
Open Channel Block ◽  
Ion Interactions ◽  
Dependent Rate ◽  
Activation Gate ◽  
Voltage Dependent ◽  
Primary Activation ◽  
Closed Pore

Classical electrophysiology and contemporary crystallography suggest that the activation gate of voltage-dependent channels is on the intracellular side, but a more extracellular “pore gate” has also been proposed. We have used the voltage dependence of block by extracellular Y3+ as a tool to locate the activation gate of the α1G (CaV3.1) T-type calcium channel. Y3+ block exhibited no clear voltage dependence from −40 to +40 mV (50% block at 25 nM), but block was relieved rapidly by stronger depolarization. Reblock of the open channel, reflected in accelerated tail currents, was fast and concentration dependent. Closed channels were also blocked by Y3+ at a concentration-dependent rate, only eightfold slower than open-channel block. When extracellular Ca2+ was replaced with Ba2+, the rate of open block by Y3+ was unaffected, but closed block was threefold faster than in Ca2+, suggesting the slower closed-block rate reflects ion–ion interactions in the pore rather than an extracellularly located gate. Since an extracellular blocker can rapidly enter the closed pore, the primary activation gate must be on the intracellular side of the selectivity filter.

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