scholarly journals Molecular basis of proton block of L-type Ca2+ channels.

1996 ◽  
Vol 108 (5) ◽  
pp. 363-374 ◽  
Author(s):  
X H Chen ◽  
I Bezprozvanny ◽  
R W Tsien
Keyword(s):  
Divalent Cations ◽  
Site Directed Mutagenesis ◽  
Protonation Site ◽  
Voltage Gated ◽  
High Conductance State ◽  
Conductance States ◽  
Acting In Concert ◽  
Ca2 Channels ◽  
Conductance State ◽  
High Conductance

Hydrogen ions are important regulators of ion flux through voltage-gated Ca2+ channels but their site of action has been controversial. To identify molecular determinants of proton block of L-type Ca2+ channels, we combined site-directed mutagenesis and unitary current recordings from wild-type (WT) and mutant L-type Ca2+ channels expressed in Xenopus oocytes. WT channels in 150 mM K+ displayed two conductance states, deprotonated (140 pS) and protonated (45 pS), as found previously in native L-type Ca2+ channels. Proton block was altered in a unique fashion by mutation of each of the four P-region glutamates (EI-EIV) that form the locus of high affinity Ca2+ interaction. Glu(E)-->Gln(Q) substitution in either repeats I or III abolished the high-conductance state, as if the titration site had become permanently protonated. While the EIQ mutant displayed only an approximately 40 pS conductance, the EIIIQ mutant showed the approximately 40 pS conductance plus additional pH-sensitive transitions to an even lower conductance level. The EIVQ mutant exhibited the same deprotonated and protonated conductance states as WT, but with an accelerated rate of deprotonation. The EIIQ mutant was unusual in exhibiting three conductance states (approximately 145, 102, 50 pS, respectively). Occupancy of the low conductance state increased with external acidification, albeit much higher proton concentration was required than for WT. In contrast, the equilibrium between medium and high conductance levels was apparently pH-insensitive. We concluded that the protonation site in L-type Ca2+ channels lies within the pore and is formed by a combination of conserved P-region glutamates in repeats I, II, and III, acting in concert. EIV lies to the cytoplasmic side of the site but exerts an additional stabilizing influence on protonation, most likely via electrostatic interaction. These findings are likely to hold for all voltage-gated Ca2+ channels and provide a simple molecular explanation for the modulatory effect of H+ ions on open channel flux and the competition between H+ ions and permeant divalent cations. The characteristics of H+ interactions advanced our picture of the functional interplay between P-region glutamates, with important implications for the mechanism of Ca2+ selectivity and permeation.

Non-voltage-gated calcium channels in snail heart ventricle cells

1990 ◽  
Vol 150 (1) ◽  
pp. 187-203
Author(s):  
B. L. Brezden ◽  
D. R. Gardner
Keyword(s):  
Dwell Time ◽  
Lymnaea Stagnalis ◽  
Divalent Cations ◽  
Voltage Sensitivity ◽  
Time Constants ◽  
Voltage Gated ◽  
Wide Range ◽  
Heart Muscle Cells ◽  
Conductance States ◽  
Ca2 Channels

1. Two recently identified channel types in Lymnaea stagnalis heart muscle cells were shown to conduct Na+ in the absence of extracellular Ca2+. They did not appear to be ‘voltage-gated’ as they were not activated by voltage. Also, they remained active over a wide range of membrane potentials. However, they were weakly ‘voltage-sensitive’ as their activity usually tended to increase with depolarization. The weak voltage-sensitivity and similarity to other non-voltagegated Ca2+ channels suggested that one or both of these channels may be receptor-operated Ca2+ channels. 2. One of the two channels had a slope conductance of 15 pS. The other appeared to have at least two subconductance states with slope conductances of 50 and 72pS. Both these conductance states had very similar open dwell-time constants and identical reversal potentials. The open dwell-time constants of both conductance states were not affected by voltage, suggesting that the channels' weak voltage-sensitivity was mediated by one of the closed states. 3. With divalent cations in the patch pipette, non-voltage-gated Ba2+ and Ca2+ currents were also detected. The Ba2+ conductance (12pS) was similar to the Ca2+ conductance (11pS).

scholarly journals Synaptic plasticity through activation of GluA3-containing AMPA-receptors

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Maria C Renner ◽  
Eva HH Albers ◽  
Nicolas Gutierrez-Castellanos ◽  
Niels R Reinders ◽  
Aile N van Huijstee ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Adrenergic Receptors ◽  
Pyramidal Neurons ◽  
Synaptic Potentiation ◽  
High Conductance State ◽  
Hippocampal Synapses ◽  
Β Adrenergic Receptors ◽  
Camp Levels ◽  
Conductance State ◽  
High Conductance

Excitatory synaptic transmission is mediated by AMPA-type glutamate receptors (AMPARs). In CA1 pyramidal neurons of the hippocampus two types of AMPARs predominate: those that contain subunits GluA1 and GluA2 (GluA1/2), and those that contain GluA2 and GluA3 (GluA2/3). Whereas subunits GluA1 and GluA2 have been extensively studied, the contribution of GluA3 to synapse physiology has remained unclear. Here we show in mice that GluA2/3s are in a low-conductance state under basal conditions, and although present at synapses they contribute little to synaptic currents. When intracellular cyclic AMP (cAMP) levels rise, GluA2/3 channels shift to a high-conductance state, leading to synaptic potentiation. This cAMP-driven synaptic potentiation requires the activation of both protein kinase A (PKA) and the GTPase Ras, and is induced upon the activation of β-adrenergic receptors. Together, these experiments reveal a novel type of plasticity at CA1 hippocampal synapses that is expressed by the activation of GluA3-containing AMPARs.

Cross-Correlations in High-Conductance States of a Model Cortical Network

2010 ◽  
Vol 22 (2) ◽  
pp. 427-447 ◽  
Author(s):  
John Hertz
Keyword(s):  
Correlation Coefficients ◽  
Neuronal Firing ◽  
Synaptic Conductance ◽  
Synaptic Currents ◽  
High Conductance State ◽  
Systematic Behavior ◽  
Cross Correlations ◽  
Conductance States ◽  
Simple Network ◽  
High Conductance

Neuronal firing correlations are studied using simulations of a simple network model for a cortical column in a high-conductance state with dynamically balanced excitation and inhibition. Although correlations between individual pairs of neurons exhibit considerable heterogeneity, population averages show systematic behavior. When the network is in a stationary state, the average correlations are generically small: correlation coefficients are of order 1/N, where N is the number of neurons in the network. However, when the input to the network varies strongly in time, much larger values are found. In this situation, the network is out of balance, and the synaptic conductance is low, at times when the strongest firing occurs. However, examination of the correlation functions of synaptic currents reveals that after these bursts, balance is restored within a few milliseconds by a rapid increase in inhibitory synaptic conductance. These findings suggest an extension of the notion of the balanced state to include balanced fluctuations of synaptic currents, with a characteristic timescale of a few milliseconds.

scholarly journals Stochastic inference with spiking neurons in the high-conductance state

2016 ◽  
Vol 94 (4) ◽  
Author(s):  
Mihai A. Petrovici ◽  
Johannes Bill ◽  
Ilja Bytschok ◽  
Johannes Schemmel ◽  
Karlheinz Meier
Keyword(s):  
Spiking Neurons ◽  
High Conductance State ◽  
Stochastic Inference ◽  
Conductance State ◽  
High Conductance

scholarly journals High-conductance state

Scholarpedia ◽  
2007 ◽  
Vol 2 (11) ◽  
pp. 1341 ◽  
Author(s):  
Alain Destexhe
Keyword(s):  
High Conductance State ◽  
Conductance State ◽  
High Conductance

Is the mammalian porin channel, VDAC, a perfect cylinder in the high conductance state?

FEBS Letters ◽  
1997 ◽  
Vol 416 (2) ◽  
pp. 187-189 ◽  
Author(s):  
C.M.M Carneiro ◽  
O.V Krasilnikov ◽  
L.N Yuldasheva ◽  
A.C Campos de Carvalho ◽  
R.A Nogueira
Keyword(s):  
High Conductance State ◽  
Conductance State ◽  
High Conductance

scholarly journals Proton Sensing of CLC-0 Mutant E166D

2005 ◽  
Vol 127 (1) ◽  
pp. 51-66 ◽  
Author(s):  
Sonia Traverso ◽  
Giovanni Zifarelli ◽  
Rita Aiello ◽  
Michael Pusch
Keyword(s):  
Persistent Current ◽  
Open Probability ◽  
Inward Current ◽  
High Conductance State ◽  
Order Of Magnitude ◽  
Cl Channels ◽  
The Common ◽  
Open States ◽  
Conductance State ◽  
High Conductance

CLC Cl− channels are homodimers in which each subunit has a proper pore and a (fast) gate. An additional slow gate acts on both pores. A conserved glutamate (E166 in CLC-0) is a major determinant of gating in CLC-0 and is crucially involved in Cl−/H+ antiport of CLC-ec1, a CLC of known structure. We constructed tandem dimers with one wild-type (WT) and one mutant subunit (E166A or E166D) to show that these mutations of E166 specifically alter the fast gate of the pore to which they belong without effect on the fast gate of the neighboring pore. In addition both mutations activate the common slow gate. E166A pores have a large, voltage-independent open probability of the fast gate (popen), whereas popen of E166D pores is dramatically reduced. Similar to WT, popen of E166D was increased by lowering pHint. At negative voltages, E166D presents a persistent inward current that is blocked by p-chlorophenoxy-acetic acid (CPA) and increased at low pHext. The pHext dependence of the persistent current is analogous to a similar steady inward current in WT CLC-0. Surprisingly, however, the underlying unitary conductance of the persistent current in E166D is about an order of magnitude smaller than that of the transient deactivating inward Cl− current. Collectively, our data support the possibility that the mutated CLC-0 channel E166D can assume two distinct open states. Voltage-independent protonation of D166 from the outside favors a low conductance state, whereas protonation from the inside favors the high conductance state.

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