scholarly journals Disrupting information coding via block of 4-AP-sensitive potassium channels

2014 ◽  
Vol 112 (5) ◽  
pp. 1054-1066 ◽  
Author(s):  
Krishnan Padmanabhan ◽  
Nathaniel N. Urban
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Single Type ◽  
Mitral Cells ◽  
Variable Expression ◽  
Neuronal Coding ◽  
Output Spike ◽  
Voltage Gated Ion Channels ◽  
Spike Patterns

Recent interest has emerged on the role of intrinsic biophysical diversity in neuronal coding. An important question in neurophysiology is understanding which voltage-gated ion channels are responsible for this diversity and how variable expression or activity of one class of ion channels across neurons of a single type affects they way populations carry information. In mitral cells in the olfactory bulb of mice, we found that biophysical diversity was conferred in part by 4-aminopyridine (4-AP)-sensitive potassium channels and reduced following block of those channels. When populations of mitral cells were stimulated with identical inputs, the diversity exhibited in their output spike patterns reduced with the addition of 4-AP, decreasing the stimulus information carried by ensembles of 15 neurons from 437 ± 15 to 397 ± 19 bits/s. Decreases in information were due to reduction in the diversity of population spike patterns generated in response to different features of the stimulus, suggesting that the coding capacity of a population can be altered by changes in the function of single ion channel types.

scholarly journals Immobilizing the Moving Parts of Voltage-Gated Ion Channels

2000 ◽  
Vol 116 (3) ◽  
pp. 461-476 ◽  
Author(s):  
Richard Horn ◽  
Shinghua Ding ◽  
Hermann J. Gruber
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Sodium Channel ◽  
Ultraviolet Irradiation ◽  
Voltage Sensors ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
S4 Segment ◽  
Moving Parts ◽  
Gated Ion Channels

Voltage-gated ion channels have at least two classes of moving parts, voltage sensors that respond to changes in the transmembrane potential and gates that create or deny permeant ions access to the conduction pathway. To explore the coupling between voltage sensors and gates, we have systematically immobilized each using a bifunctional photoactivatable cross-linker, benzophenone-4-carboxamidocysteine methanethiosulfonate, that can be tethered to cysteines introduced into the channel protein by mutagenesis. To validate the method, we first tested it on the inactivation gate of the sodium channel. The benzophenone-labeled inactivation gate of the sodium channel can be trapped selectively either in an open or closed state by ultraviolet irradiation at either a hyperpolarized or depolarized voltage, respectively. To verify that ultraviolet light can immobilize S4 segments, we examined its relative effects on ionic and gating currents in Shaker potassium channels, labeled at residue 359 at the extracellular end of the S4 segment. As predicted by the tetrameric stoichiometry of these potassium channels, ultraviolet irradiation reduces ionic current by approximately the fourth power of the gating current reduction, suggesting little cooperativity between the movements of individual S4 segments. Photocross-linking occurs preferably at hyperpolarized voltages after labeling residue 359, suggesting that depolarization moves the benzophenone adduct out of a restricted environment. Immobilization of the S4 segment of the second domain of sodium channels prevents channels from opening. By contrast, photocross-linking the S4 segment of the fourth domain of the sodium channel has effects on both activation and inactivation. Our results indicate that specific voltage sensors of the sodium channel play unique roles in gating, and suggest that movement of one voltage sensor, the S4 segment of domain 4, is at least a two-step process, each step coupled to a different gate.

Zinc and Copper Influence Excitability of Rat Olfactory Bulb Neurons by Multiple Mechanisms

2001 ◽  
Vol 86 (4) ◽  
pp. 1652-1660 ◽  
Author(s):  
Michelle S. Horning ◽  
Paul Q. Trombley
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Olfactory Bulb ◽  
Membrane Potentials ◽  
Repetitive Firing ◽  
Delayed Rectifier ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Olfactory Bulb Neurons ◽  
Gated Ion Channels

Zinc and copper are highly concentrated in several mammalian brain regions, including the olfactory bulb and hippocampus. Whole cell electrophysiological recordings were made from rat olfactory bulb neurons in primary culture to compare the effects of zinc and copper on synaptic transmission and voltage-gated ion channels. Application of either zinc or copper eliminated GABA-mediated spontaneous inhibitory postsynaptic potentials. However, in contrast to the similarity of their effects on inhibitory transmission, spontaneous glutamate-mediated excitatory synaptic activity was completely blocked by copper but only inhibited by zinc. Among voltage-gated ion channels, zinc or copper inhibited TTX-sensitive sodium channels and delayed rectifier-type potassium channels but did not prevent the firing of evoked single action potentials or dramatically alter their kinetics. Zinc and copper had distinct effects on transient A-type potassium currents. Whereas copper only inhibited the A-type current, zinc modulation of A-type currents resulted in either potentiation or inhibition of the current depending on the membrane potential. The effects of zinc and copper on potassium channels likely underlie their effects on repetitive firing in response to long-duration step depolarizations. Copper reduced repetitive firing independent of the initial membrane voltage. In contrast, whereas zinc reduced repetitive firing at membrane potentials associated with zinc-mediated enhancement of the A-type current (−50 mV), in a significant proportion of neurons, zinc increased repetitive firing at membrane potentials associated with zinc-mediated inhibition of the A-type current (−90 mV). Application of zinc or copper also inhibited voltage-gated Ca2+ channels, suggesting a possible role for presynaptic modulation of neurotransmitter release. Despite similarities between the effects of zinc and copper on some ligand- and voltage-gated ion channels, these data suggest that their net effects likely contribute to differential modulation of neuronal excitability.

scholarly journals Multilayer Processing of Spatiotemporal Spike Patterns in a Neuron with Active Dendrites

2010 ◽  
Vol 22 (8) ◽  
pp. 2086-2112 ◽  
Author(s):  
Yingxue Wang ◽  
Shih-Chii Liu
Keyword(s):  
Large Scale ◽  
Spatial Clustering ◽  
Active Role ◽  
Temporal Synchrony ◽  
Active Dendrites ◽  
Nmda Channels ◽  
Voltage Gated Ion Channels ◽  
Spike Patterns ◽  
Input Spike

With the advent of new experimental evidence showing that dendrites play an active role in processing a neuron's inputs, we revisit the question of a suitable abstraction for the computing function of a neuron in processing spatiotemporal input patterns. Although the integrative role of a neuron in relation to the spatial clustering of synaptic inputs can be described by a two-layer neural network, no corresponding abstraction has yet been described for how a neuron processes temporal input patterns on the dendrites. We address this void using a real-time aVLSI (analog very-large-scale-integrated) dendritic compartmental model, which incorporates two widely studied classes of regenerative event mechanisms: one is mediated by voltage-gated ion channels and the other by transmitter-gated NMDA channels. From this model, we find that the response of a dendritic compartment can be described as a nonlinear sigmoidal function of both the degree of input temporal synchrony and the synaptic input spatial clustering. We propose that a neuron with active dendrites can be modeled as a multilayer network that selectively amplifies responses to relevant spatiotemporal input spike patterns.

scholarly journals Domain–domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Mark A Zaydman ◽  
Marina A Kasimova ◽  
Kelli McFarland ◽  
Zachary Beller ◽  
Panpan Hou ◽  
...  
Keyword(s):  
Ion Channels ◽  
Physiological Role ◽  
Specific Expression ◽  
Electrical Currents ◽  
Voltage Gated ◽  
State Dependent ◽  
Domain Interactions ◽  
Voltage Gated Ion Channels ◽  
Hormonal Release

Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (<xref ref-type="bibr" rid="bib3">Barhanin et al., 1996</xref>; <xref ref-type="bibr" rid="bib57">Sanguinetti et al., 1996</xref>), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (<xref ref-type="bibr" rid="bib77">Wrobel et al., 2012</xref>; <xref ref-type="bibr" rid="bib66">Sun et al., 2012</xref>; <xref ref-type="bibr" rid="bib1">Abbott, 2014</xref>). These changes are essential for the physiological role of IKs (<xref ref-type="bibr" rid="bib62">Silva and Rudy, 2005</xref>); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore.

scholarly journals Analysis of Single Nucleotide Polymorphisms in human Voltage-Gated Ion Channels

2018 ◽  
Author(s):  
Katerina C. Nastou ◽  
Michail A. Batskinis ◽  
Zoi I. Litou ◽  
Stavros J. Hamodrakas ◽  
Vassiliki A. Iconomidou
Keyword(s):  
Ion Channels ◽  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Topological Information ◽  
Single Nucleotide ◽  
Voltage Gated ◽  
Arginine Residues ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

AbstractVoltage-Gated Ion Channels (VGICs) are one of the largest groups of transmembrane proteins. Due to their major role in the generation and propagation of electrical signals, VGICs are considered important from a medical viewpoint and their dysfunction is often associated with a group of diseases known as “Channelopathies”. We identified disease associated mutations and polymorphisms in these proteins through mapping missense Single Nucleotide Polymorphisms (SNPs) from the UniProt and ClinVar databases on their amino acid sequence, taking into consideration their special topological and functional characteristics. Statistical analysis revealed that disease associated SNPs are mostly found in the Voltage Sensor Domain – and especially at its fourth transmembrane segment (S4) – and in the Pore Loop. Both these regions are extremely important for the activation and ion conductivity of VGICs. Moreover, amongst the most frequently observed mutations are those of arginine to glutamine, to histidine or to cysteine, which can probably be attributed to the extremely important role of arginine residues in the regulation of membrane potential in these proteins. We suggest that topological information in combination with genetic variation data can contribute towards a better evaluation of the effect of currently unclassified mutations in VGICs. It is hoped that potential associations with certain disease phenotypes will be revealed in the future, with the use of similar approaches.

International Union of Pharmacology. XLI. Compendium of Voltage-Gated Ion Channels: Potassium Channels

2003 ◽  
Vol 55 (4) ◽  
pp. 583-586 ◽  
Author(s):  
George A. Gutman ◽  
K. George Chandy ◽  
John P. Adelman ◽  
Jayashree Aiyar ◽  
Douglas A. Bayliss ◽  
...  
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
International Union ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals Potassium channels as potential drug targets for limb wound repair and regeneration

2019 ◽  
Vol 3 (1) ◽  
pp. 22-33
Author(s):  
Wengeng Zhang ◽  
Pragnya Das ◽  
Sarah Kelangi ◽  
Marianna Bei
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Drug Targets ◽  
Wound Repair ◽  
Limb Regeneration ◽  
Large Family ◽  
Potential Drug ◽  
Mouse Limb ◽  
Potential Drug Targets

Abstract Background Ion channels are a large family of transmembrane proteins, accessible by soluble membrane-impermeable molecules, and thus are targets for development of therapeutic drugs. Ion channels are the second most common target for existing drugs, after G protein-coupled receptors, and are expected to make a big impact on precision medicine in many different diseases including wound repair and regeneration. Research has shown that endogenous bioelectric signaling mediated by ion channels is critical in non-mammalian limb regeneration. However, the role of ion channels in regeneration of limbs in mammalian systems is not yet defined. Methods To explore the role of potassium channels in limb wound repair and regeneration, the hindlimbs of mouse embryos were amputated at E12.5 when the wound is expected to regenerate and E15.5 when the wound is not expected to regenerate, and gene expression of potassium channels was studied. Results Most of the potassium channels were downregulated, except for the potassium channel kcnj8 (Kir6.1) which was upregulated in E12.5 embryos after amputation. Conclusion This study provides a new mouse limb regeneration model and demonstrates that potassium channels are potential drug targets for limb wound healing and regeneration.

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