scholarly journals CORRELATIONAL PATCH-CLAMP SPECTROMETRY OF THE ION CHANNELS

2017 ◽  
Author(s):  
Oleg Gradov
Keyword(s):  
Ion Channels ◽  
Patch Clamp ◽  
Ion Channel ◽  
Conformational Changes ◽  
Metal Ion ◽  
Ion Selectivity ◽  
Special Kind ◽  
Channel Structure ◽  
Spectral Processing ◽  
Electrophysiological Response

Membrane ion channels operate in accordance with the main principles of coordination chemistry. Coordination number is known to determine the ion selectivity of the sodium and potassium channels. there are known both ligand-dependent and ligand-controlled ion channels operating within the supramolecular coordination fixation principles. The channel-forming ionophores form the structures which bind cations via coordination bonds leading to the conformational changes with the adjustment of the whole supramolecular architecture providing the ion channel selectivity. Such kind of non-covalent systems underlie the electrogenic membrane functions and the potential-controlled transmembrane ion transfer systems. They can be studied by means of the path-clamp method (i.e. the local membrane potential fixation), such as the «anion clamp», applied together with the analysis of the metal ion coordination geometry with the ion channels. However, such methods are not capable to register the ion channel conformational state in situ - during the ion coordination - with the molecular resolution of the ion channel structure. In this regard there is a need to develop dynamical methods capable of the simultaneous registration of the conformational and metallomic / elementomic coordination parameters and the electrophysiological response to the ion coordination. We propose to develop for this purpose a special kind of spectroscopic systems providing registration of the electrophysiological parameters and the single ion channel response by means of the local potential fixation techniques (patch-clamp / voltage-clamp) with the advanced spectral processing and the subsequent data mining, with the simultaneous spectral detection of the ion channel state as a coordination and conformationally labile supramolecular structure, with the final data processing results presented not as the single spectra, but as the spectral correlogram.Градов О. В., Орехов Ф. К. Корреляционная патч-кламп-спектрометрия ионных каналов – сочетание спектрального анализа электрофизиологического отклика каналома в нежестком реальном времени и методов спектроскопии ионных каналов как координационных (комплексных) структур // Биомедицинская инженерия и электроника. — 2016. — № 2(13). — С. 5–28.

Ion Channels in Plants

2012 ◽  
Vol 92 (4) ◽  
pp. 1777-1811 ◽  
Author(s):  
Rainer Hedrich
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Patch Clamp ◽  
Ion Channel ◽  
Potassium Channel ◽  
Guard Cells ◽  
Channel Structure ◽  
Model Systems ◽  
Dependent Manner ◽  
Inward Rectifiers

Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type- and cell membrane-dependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K+-selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K+ channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow- and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.

Simulation approaches to ion channel structure–function relationships

2001 ◽  
Vol 34 (4) ◽  
pp. 473-561 ◽  
Author(s):  
D. Peter Tieleman ◽  
Phil C. Biggin ◽  
Graham R. Smith ◽  
Mark S. P. Sansom
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Ion Selectivity ◽  
Mean Field ◽  
Transport Processes ◽  
Channel Structure ◽  
Potential Profile ◽  
Model Systems ◽  
Atomistic Simulations ◽  
K Channels

1. Introduction 4751.1 Ion channels 4751.1.1 Gramicidin 4761.1.2 Helix bundle channels 4771.1.3 K channels 4801.1.4 Porins 4831.1.5 Nicotinic acetylcholine receptor 4831.1.6 Physiological properties 4831.2 Simulations 4841.2.1 Atomistic versus mean-field simulations 4842. Atomistic simulations 4852.1 Modelling of ion-interaction parameters 4852.1.1 Interatomic distances and the problem of ionic radii 4862.1.2 Solvation energy 4872.1.3 Hydration shells and coordination numbers 4892.1.4 Parameters in common use and transferability 4912.1.5 Summary 4912.2 Water in pores versus bulk 4912.2.1 Simple pore models 4942.2.2 gA 4952.2.3 Alm 4962.2.4 LS36 (and LS24) 4962.2.5 Nicotinic receptor M2δ5 4972.2.6 Influenza A M2 4972.2.7 K channels 4972.2.8 nAChR 4982.2.9 Porins 4982.2.10 Relevance 4992.2.11 Problems with simulations 5012.3 Dynamics of ions in pores 5032.3.1 Simple pore models 5032.3.2 Helix bundles 5042.3.3 gA and KcsA 5052.4 Energetics of permeation and ion selectivity 5092.4.1 Potential and free energy profiles 5092.4.2 gA 5102.4.3 α-Helix bundles 5112.4.4 KcsA 5122.4.5 Ion selectivity 5142.4.6 Problems of estimating energetic profiles 5152.5 Conformational changes 5162.5.1 gA 5162.5.2 Alm and LS3 5162.5.3 KcsA 5172.6 Protonation states 5233. Coarse-grained simulations 5243.1 Introduction 5243.1.1 Predicting conductance magnitudes 5253.2 Electro-diffusion: the Nernst–Planck approach 5263.2.1 Calculating the potential profile from Poisson and PB theory 5283.2.2 Calculating the potential profile from BD simulations 5303.2.3 Combining Nernst–Planck and Poisson: PNP 5303.3 Beyond PNP 5323.4 BD simulations 5323.4.1 Basic theory in ion channels 5323.4.2 Incorporating the environment 5333.5 Applications 5353.5.1 Model systems 5353.5.1.1 Solving the Poisson and PB equation for channel-like geometries 5353.5.1.2 Comparing PB, PNP and BD 5363.5.2 Applications to known structures 5373.5.2.1 gA 5373.5.2.2 Porin 5393.5.2.3 LS3 5403.5.2.4 Alm 5423.5.2.5 nAChR 5423.5.2.6 KcsA 5433.6 pKa calculations 5433.7 Selectivity 5443.7.1 Anion/cation selectivity 5453.7.2 Monovalent/divalent ion selectivity 5454. Problems 5464.1 Atomistic simulations 5464.1.1 Problems 5464.1.2 Parameters 5484.2 BD 5494.3 Mean-field simulations 5495. Conclusions 5505.1 Progress 5505.2 The future 5506. Acknowledgements 5517. References 551Ion channels are proteins that form ‘holes’ in membranes through which selected ions move passively down their electrochemical gradients. The ions move quickly, at (nearly) diffusion limited rates (ca. 107 ions s−1 per channel). Ion channels are central to many properties of cell membranes. Traditionally they have been the concern of neuroscientists, as they control the electrical properties of the membranes of excitable cells (neurones, muscle; Hille, 1992). However, it is evident that ion channels are present in many types of cell, not all of which are electrically excitable, from diverse organisms, including plants, bacteria and viruses (where they are involved in functions such as cell homeostasis) in addition to animals. Thus ion channels are of general cell biological importance. They are also of biomedical interest, as several dizeases (‘channelopathies’) have been described which are caused by changes in properties of a specific ion channel (Ashcroft, 2000). Moreover, passive diffusion channels for substances other than ions are common (porins, aquaporins), as are active membrane transport processes coupled to ion gradients or ATP hydrolysis. An understanding of ion channels may also provide a gateway to understanding these processes.

Ion channel activities of cultured rat mesangial cells

1991 ◽  
Vol 261 (5) ◽  
pp. F808-F814 ◽  
Author(s):  
H. Matsunaga ◽  
N. Yamashita ◽  
Y. Miyajima ◽  
T. Okuda ◽  
H. Chang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ion Channels ◽  
Patch Clamp ◽  
Ion Channel ◽  
Arginine Vasopressin ◽  
Mesangial Cells ◽  
Cation Channel ◽  
K Channel ◽  
Patch Clamp Technique ◽  
Inside Out

We used the patch-clamp technique to clarify the nature of ion channels in renal mesangial cells in culture. In the cell-attached mode most patches were silent in the absence of agonists. In some patches a 25-pS nonselective channel was observed. This 25-pS cation channel was consistently observed in inside-out patches, and it was activated by intracellular Ca2+. Excised patch experiments also revealed the existence of a 40-pS K+ channel, which was activated by intracellular Ca2+. This 40-pS K+ channel was observed infrequently in the cell-attached mode. The activities of both channels were increased by arginine vasopressin or angiotensin II, resulting from an increase in intracellular Ca2+ concentration.

scholarly journals Computational Ion Channel Research: from the Application of Artificial Intelligence to Molecular Dynamics Simulations.

2020 ◽  
Vol 55 (S3) ◽  
pp. 14-45
Keyword(s):  
Artificial Intelligence ◽  
Molecular Dynamics ◽  
Ion Channels ◽  
Ion Channel ◽  
Computational Methods ◽  
Homology Modelling ◽  
Channel Structure ◽  
Learning Approaches ◽  
Qsar Analysis ◽  
Wide Range

Although ion channels are crucial in many physiological processes and constitute an important class of drug targets, much is still unclear about their function and possible malfunctions that lead to diseases. In recent years, computational methods have evolved into important and invaluable approaches for studying ion channels and their functions. This is mainly due to their demanding mechanism of action where a static picture of an ion channel structure is often insufficient to fully understand the underlying mechanism. Therefore, the use of computational methods is as important as chemical-biological based experimental methods for a better understanding of ion channels. This review provides an overview on a variety of computational methods and software specific to the field of ion-channels. Artificial intelligence (or more precisely machine learning) approaches are applied for the sequence-based prediction of ion channel family, or topology of the transmembrane region. In case sufficient data on ion channel modulators is available, these methods can also be applied for quantitative structureactivity relationship (QSAR) analysis. Molecular dynamics (MD) simulations combined with computational molecular design methods such as docking can be used for analysing the function of ion channels including ion conductance, different conformational states, binding sites and ligand interactions, and the influence of mutations on their function. In the absence of a three-dimensional protein structure, homology modelling can be applied to create a model of your ion channel structure of interest. Besides highlighting a wide range of successful applications, we will also provide a basic introduction to the most important computational methods and discuss best practices to get a rough idea of possible applications and risks.

Ion Channel Permeation and Selectivity

2019 ◽  
Author(s):  
Juan J. Nogueira ◽  
Ben Corry
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Ion Selectivity ◽  
Ionic Currents ◽  
Biological Processes ◽  
Ion Permeation ◽  
Voltage Gated ◽  
Physical Mechanisms ◽  
Theoretical Approaches ◽  
Mechanistic Insight

Many biological processes essential for life rely on the transport of specific ions at specific times across cell membranes. Such exquisite control of ionic currents, which is regulated by protein ion channels, is fundamental for the proper functioning of the cells. It is not surprising, therefore, that the mechanism of ion permeation and selectivity in ion channels has been extensively investigated by means of experimental and theoretical approaches. These studies have provided great mechanistic insight but have also raised new questions that are still unresolved. This chapter first summarizes the main techniques that have provided significant knowledge about ion permeation and selectivity. It then discusses the physical mechanisms leading to ion permeation and the explanations that have been proposed for ion selectivity in voltage-gated potassium, sodium, and calcium channels.

scholarly journals An improved open-channel structure of MscL determined from FRET confocal microscopy and simulation

2010 ◽  
Vol 136 (4) ◽  
pp. 483-494 ◽  
Author(s):  
Ben Corry ◽  
Annette C. Hurst ◽  
Prithwish Pal ◽  
Takeshi Nomura ◽  
Paul Rigby ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Conformational Changes ◽  
Brownian Dynamics ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Channel Structure ◽  
Paramagnetic Resonance ◽  
Physiological Processes ◽  
Lipid Environment ◽  
Dynamics Simulations

Mechanosensitive channels act as molecular transducers of mechanical force exerted on the membrane of living cells by opening in response to membrane bilayer deformations occurring in physiological processes such as touch, hearing, blood pressure regulation, and osmoregulation. Here, we determine the likely structure of the open state of the mechanosensitive channel of large conductance using a combination of patch clamp, fluorescence resonance energy transfer (FRET) spectroscopy, data from previous electron paramagnetic resonance experiments, and molecular and Brownian dynamics simulations. We show that structural rearrangements of the protein can be measured in similar conditions as patch clamp recordings while controlling the state of the pore in its natural lipid environment by modifying the lateral pressure distribution via the lipid bilayer. Transition to the open state is less dramatic than previously proposed, while the N terminus remains anchored at the surface of the membrane where it can either guide the tilt of or directly translate membrane tension to the conformation of the pore-lining helix. Combining FRET data obtained in physiological conditions with simulations is likely to be of great value for studying conformational changes in a range of multimeric membrane proteins.

WHAT CAUSES ION CHANNEL PROTEINS TO FLUCTUATE OPEN AND CLOSED?

1996 ◽  
Vol 07 (04) ◽  
pp. 321-331 ◽  
Author(s):  
LARRY S. LIEBOVITCH ◽  
ANGELO T. TODOROV
Keyword(s):  
Ion Channels ◽  
Patch Clamp ◽  
Ion Channel ◽  
Patch Clamp Technique ◽  
Sodium Potassium ◽  
Random Event ◽  
Channel Protein ◽  
Channel Proteins ◽  
Ion Channel Proteins ◽  
Open States

Ion channels in the cell membrane spontaneously switch from states that are closed to the flow of ions such as sodium, potassium, and chloride to states that are open to the flow of these ions. The durations of times that an individual ion channel protein spends in the closed and open states can be measured by the patch clamp technique. We explore two basic issues about the molecular properties of ion channels: 1) If the switching between the closed and open state is an inherently random event, what does the patch clamp data tell us about the structure or motions in the ion channel protein? 2) Is this switching random?

Ion channels and disease

2020 ◽  
pp. 246-255
Author(s):  
Frances Ashcroft ◽  
Paolo Tammaro
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Single Channel ◽  
Cell Types ◽  
Channel Structure ◽  
Channel Proteins ◽  
Channel Function ◽  
Ion Channel Proteins ◽  
Single Channel Currents ◽  
Channel Currents

Ion channels are membrane proteins that act as gated pathways for the movement of ions across cell membranes. They are found in both surface and intracellular membranes and play essential roles in the physiology of all cell types. An ever-increasing number of human diseases are now known to be caused by defects in ion channel function. To understand how ion channel defects give rise to disease, it is helpful to understand how the ion channel proteins work. This chapter therefore considers what is known of ion channel structure, explains the properties of the single ion channel, and shows how single-channel currents give rise to action potentials and synaptic potentials.

The Cys-loop superfamily of ligand-gated ion channels: the impact of receptor structure on function

2004 ◽  
Vol 32 (3) ◽  
pp. 529-534 ◽  
Author(s):  
C.N. Connolly ◽  
K.A. Wafford
Keyword(s):  
Ion Channels ◽  
Conformational Changes ◽  
Channel Structure ◽  
Channel Function ◽  
Receptor Structure ◽  
Channel Opening ◽  
The Impact ◽  
Ion Pore ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

The Cys-loop receptors constitute an important superfamily of LGICs (ligand-gated ion channels) comprising receptors for acetylcholine, 5-HT3 (5-hydroxytryptamine; 5-HT3 receptors), glycine and GABA (γ-aminobutyric acid; GABAA receptors). A vast knowledge of the structure of the Cys-loop superfamily and its impact on channel function have been accrued over the last few years, leading to exciting new proposals on how ion channels open and close in response to agonist binding. Channel opening is initiated by the extracellular association of agonists to discrete binding pockets, leading to dramatic conformational changes, culminating in the opening of a central ion pore. The importance of channel structure is exemplified in the allosteric modulation of channel function by the binding of other molecules to distinct sites on the channel, which exerts an additional level of control on their function. The subsequent conformational changes (gating) lead to channel opening and ion transport. Following channel pore opening, ion selectivity is determined by receptor structure in, and around, the ion pore. As a final level of control, cytoplasmic determinants control the magnitude (conductance) of ion flow into the cell. Thus the Cys-loop receptors are complex molecular motors, with moving parts, which can transduce extracellular signals across the plasma membrane. Once the full mechanical motions involved are understood, it may be possible to design sophisticated therapeutic agents to modulate their activity, or at least be able to throw a molecular spanner into the works!

scholarly journals Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed hiPSCs to Differentiated Neuronal and Cardiac Progeny

2013 ◽  
Vol 2013 ◽  
pp. 1-25 ◽  
Author(s):  
Leonhard Linta ◽  
Marianne Stockmann ◽  
Qiong Lin ◽  
André Lechel ◽  
Christian Proepper ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Ion Selectivity ◽  
Expression Patterns ◽  
Stem Cell Differentiation ◽  
Human Keratinocytes ◽  
Ips Cells ◽  
Cellular Processes ◽  
Gating Mechanism ◽  
Channel Expression

Ion channels are involved in a large variety of cellular processes including stem cell differentiation. Numerous families of ion channels are present in the organism which can be distinguished by means of, for example, ion selectivity, gating mechanism, composition, or cell biological function. To characterize the distinct expression of this group of ion channels we have compared the mRNA expression levels of ion channel genes between human keratinocyte-derived induced pluripotent stem cells (hiPSCs) and their somatic cell source, keratinocytes from plucked human hair. This comparison revealed that 26% of the analyzed probes showed an upregulation of ion channels in hiPSCs while just 6% were downregulated. Additionally, iPSCs express a much higher number of ion channels compared to keratinocytes. Further, to narrow down specificity of ion channel expression in iPS cells we compared their expression patterns with differentiated progeny, namely, neurons and cardiomyocytes derived from iPS cells. To conclude, hiPSCs exhibit a very considerable and diverse ion channel expression pattern. Their detailed analysis could give an insight into their contribution to many cellular processes and even disease mechanisms.

Sign in / Sign up

Export Citation Format

Share Document