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Diminishing neuronal acidification by channelrhodopsins with low proton conduction.

ABSTRACT: Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK cells established that the acidification was due to proton transport through the opsin, rather than through other voltage-dependent channels. We identified and characterized two opsins which showed large photocurrents, but small proton permeability, PsCatCh2.0 and ChR2-3M. PsCatCh2.0 showed excellent response kinetics and was also spectrally compatible with simultaneous voltage imaging with QuasAr6a. Stimulation-evoked acidification is a possible source of disruptions to cell health in scientific and prospective therapeutic applications of optogenetics. Channelrhodopsins with low proton permeability are a promising strategy for avoiding these problems.

SUBMITTER: Hayward RF

PROVIDER: S-EPMC10558203 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Diminishing neuronal acidification by channelrhodopsins with low proton conduction.

Hayward Rebecca Frank RF Brooks F Phil FP Yang Shang S Gao Shiqiang S Cohen Adam E AE

eLife 20231006

Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK cells established that the acidification was due to proton transport through the opsin, rather than through other voltage-dependent channels. We identified and characterized two opsins which showed larg ...[more]

PMID: 37801078

Similar Datasets

Diminishing neuronal acidification by channelrhodopsins with low proton conduction.

Project description:Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK cells established that the acidification was due to proton transport through the opsin, rather than through other voltage-dependent channels. We identified and characterized two opsins which showed large photocurrents, but small proton permeability, PsCatCh2.0 and ChR2-3M. PsCatCh2.0 showed excellent response kinetics and was also spectrally compatible with simultaneous voltage imaging with QuasAr6a. Stimulation-evoked acidification is a possible source of disruptions to cell health in scientific and prospective therapeutic applications of optogenetics. Channelrhodopsins with low proton permeability are a promising strategy for avoiding these problems.Statement of significanceAcidification is an undesirable artifact of optogenetic stimulation. Low proton-permeability opsins minimize this artifact while still allowing robust optogenetic control.

| S-EPMC9934520 | biostudies-literature

Intramolecular proton transfer in channelrhodopsins.

Project description:Channelrhodopsins serve as photoreceptors that control the motility behavior of green flagellate algae and act as light-gated ion channels when heterologously expressed in animal cells. Here, we report direct measurements of proton transfer from the retinylidene Schiff base in several channelrhodopsin variants expressed in HEK293 cells. A fast outward-directed current precedes the passive channel current that has the opposite direction at physiological holding potentials. This rapid charge movement occurs on the timescale of the M intermediate formation in microbial rhodopsins, including that for channelrhodopsin from Chlamydomonas augustae and its mutants, reported in this study. Mutant analysis showed that the glutamate residue corresponding to Asp(85) in bacteriorhodopsin acts as the primary acceptor of the Schiff-base proton in low-efficiency channelrhodopsins. Another photoactive-site residue corresponding to Asp(212) in bacteriorhodopsin serves as an alternative proton acceptor and plays a more important role in channel opening than the primary acceptor. In more efficient channelrhodopsins from Chlamydomonas reinhardtii, Mesostigma viride, and Platymonas (Tetraselmis) subcordiformis, the fast current was apparently absent. The inverse correlation of the outward proton transfer and channel activity is consistent with channel function evolving in channelrhodopsins at the expense of their capacity for active proton transport.

| S-EPMC3576534 | biostudies-literature

High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels.

Project description:Channelrhodopsin-2 (ChR2) has become an indispensable tool in neuroscience, allowing precise induction of action potentials with short light pulses. A limiting factor for many optophysiological experiments is the relatively small photocurrent induced by ChR2. We screened a large number of ChR2 point mutants and discovered a dramatic increase in photocurrent amplitude after threonine-to-cysteine substitution at position 159. When we tested the T159C mutant in hippocampal pyramidal neurons, action potentials could be induced at very low light intensities, where currently available channelrhodopsins were unable to drive spiking. Biophysical characterization revealed that the kinetics of most ChR2 variants slows down considerably at depolarized membrane potentials. We show that the recently published E123T substitution abolishes this voltage sensitivity and speeds up channel kinetics. When we combined T159C with E123T, the resulting double mutant delivered fast photocurrents with large amplitudes and increased the precision of single action potential induction over a broad range of frequencies, suggesting it may become the standard for light-controlled activation of neurons.

| S-EPMC3088623 | biostudies-literature

Structural mechanism of proton conduction in otopetrin proton channel.

Project description:The otopetrin (OTOP) proteins were recently characterized as extracellular proton-activated proton channels. Several recent OTOP channel structures demonstrated that the channels form a dimer with each subunit adopting a double-barrel architecture. However, the structural mechanisms underlying some basic functional properties of the OTOP channels remain unresolved, including extracellular pH activation, proton conducting pathway, and rapid desensitization. In this study, we performed structural and functional characterization of the Caenorhabditis elegans OTOP8 (CeOTOP8) and mouse OTOP2 (mOTOP2) and illuminated a set of conformational changes related to the proton-conducting process in OTOP. The structures of CeOTOP8 reveal the conformational change at the N-terminal part of TM12 that renders the channel in a transiently proton-transferring state, elucidating an inter-barrel, Glu/His-bridged proton passage within each subunit. The structures of mOTOP2 reveal the conformational change at the N-terminal part of TM6 that exposes the central glutamate to the extracellular solution for protonation. In addition, the structural comparison between CeOTOP8 and mOTOP2, along with the structure-based mutagenesis, demonstrates that an inter-subunit movement at the OTOP channel dimer interface plays a central role in regulating channel activity. Combining the structural information from both channels, we propose a working model describing the multi-step conformational changes during the proton conducting process.

| S-EPMC11343839 | biostudies-literature

Aqueous proton-selective conduction across two-dimensional graphyne.

Project description:The development of direct methanol fuel cells is hindered by the issue of methanol crossover across membranes, despite the remarkable features resulting from the use of liquid fuel. Here we investigate the proton-selective conduction behavior across 2D graphyne in an aqueous environment. The aqueous proton conduction mechanism transitions from bare proton penetration to a mixed vehicular and Grotthuss transportation when the side length of triangular graphyne pores increases to 0.95 nm. A further increase in the side length to 1.2 nm results in the formation of a patterned aqueous/vacuum interphase, enabling protons to be conducted through the water wires via Grotthuss mechanism with low energy barriers. More importantly, it is found that 2D graphyne with the side length of less than 1.45 nm can effectively block methanol crossover, suggesting that 2D graphyne with an appropriate pore size is an ideal material to achieve zero-crossover proton-selective membranes.

| S-EPMC6412031 | biostudies-literature

High Surface Proton Conduction in Nanostructured ZIF-8.

Project description:The zeolitic imidazolate framework-8 (ZIF-8) combines a significantly high microporosity with an excellent thermal, chemical, and hydrothermal stability. Here, we demonstrated that ZIF-8 can display significant levels of protonic conductivity through a water-mediated surface transport mechanism associated to the presence of di-coordinated Zn ions revealed by X-ray photoelectron spectroscopy. A set of powders with particle sizes from 2.8 µm down to 80 nm studied by dynamic water vapour sorption analysis was used to demonstrate that water adsorbs predominantly in the micropore cavities of microcrystalline ZIF-8, whereas adsorption on the external surface becomes the dominant contribution for the nanostructured material. Impedance spectroscopy in turn revealed that the protonic conductivity of the nanocrystalline ZIF-8 was two orders of magnitude higher than that of the micron-sized powders, reaching approximately 0.5 mS·cm-1 at 94 °C and 98% relative humidity. Simple relations were derived in order to estimate the potential gains in water uptake and conductivity as a function of the particle size. This new strategy combining particle nanostructuring with surface defects, demonstrated here for one of the most know metal organic framework, is of general application to potentially boost the conductivity of other materials avoiding chemical functionalization strategies that in most if not all cases compromise their chemical stability, particularly under high humidity and high temperature conditions.

| S-EPMC6835583 | biostudies-literature

Exploring long-range proton conduction, the conduction mechanism and inner hydration state of protein biopolymers.

Project description:Proteins are the main proton mediators in various biological proton circuits. Using proteins for the formation of long-range proton conductors is offering a bioinspired approach for proton conductive polymers. One of the main challenges in the field of proton conductors is to explore the local environment within the polymers, along with deciphering the conduction mechanism. Here, we show that the protonic conductivity across a protein-based biopolymer can be hindered using straightforward chemical modifications, targeting carboxylate- or amine-terminated residues of the protein, as well as exploring the effect of surface hydrophobicity on proton conduction. We further use the natural tryptophan residue as a local fluorescent probe for the inner local hydration state of the protein surface and its tendency to form hydrogen bonds with nearby water molecules, along with the dynamicity of the process. Our electrical and spectroscopic measurements of the different chemically-modified protein materials as well as the material at different water-aprotic solvent mixtures result in our fundamental understanding of the proton mediators within the material and gaining important insights on the proton conduction mechanism. Our biopolymer can be used as an attractive platform for the study of bio-related protonic circuits as well as a proton conducting biopolymer for various applications, such as protonic transistors, ionic transducers and fuel cells.

| S-EPMC8152808 | biostudies-literature

Proton Conducting Membranes with Molecular Self Assemblies and Ionic Channels for Efficient Proton Conduction.

Project description:Supramolecular assemblies are vital for biological systems. This phenomenon in artificial materials is directly related to their numerous properties and their performance. Here, a simple approach to supramolecular assemblies is employed to fabricate highly efficient proton conducting molecular wires for fuel cell applications. Small molecule-based molecular assembly leading to a discotic columnar architecture is achieved, simultaneously with proton conduction that can take place efficiently in the absence of water, which otherwise is very difficult to obtain in interconnected ionic channels. High boiling point proton facilitators are incorporated into these columns possessing central ionic channels, thereby increasing the conduction multifold. Larger and asymmetrical proton facilitators disintegrated the self-assembly, resulting in low proton conduction efficiency. The highest conductivity was found to be approaching 10-2 S/cm for the molecular wires in an anhydrous state, which is ascribed to the continuous network of hydrogen bonds in which protons can hop between with a lower energy barrier. The molecular wires with ionic channels presented here have potential as an alternative to proton conductors operating under anhydrous conditions at both low and high temperatures.

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Heteroatom-embedded Mellitic Triimido COFs for efficient proton conduction.

Project description:Ionic covalent organic frameworks (iCOFs) are promising materials for energy storage devices due to their ionic functional groups, which facilitate ion transport, and their highly ordered pores of their frameworks, which provide ideal pathways for long-term ion transport under harsh electrochemical conditions. In this study, we attempted for the first time to synthesize an unprecedented iCOF using a heteroatom-embedded mellitic triimido COF framework that enables practical ion channels on the Angstrom scale. This iCOF was subsequently evaluated as an anhydrous proton-conducting material. The heterocyclic pyridine group of the 2,5-diaminopyridine (DAPy) linker plays an important role, not only as an AB stacking-inducing group but also as a proton acceptor that interacts with impregnated H3PO4. The resulting PA@MTI-DAPy-COF exhibited high proton conductivity of 3.68 × 10-2 S cm-1 at 150oC under anhydrous conditions. This work paves the way for constructing efficient proton-conducting channels by leveraging the stacking structure of COF skeletons.

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Project description:Peptides have been overlooked for their use in the field of electronics, even though they are one of the most commonly found bio-induced materials, and are not only easy to mass-produce but also exhibit a high dielectric constant. Additionally, unlike proteins, which are gaining considerable interest with materials researchers, peptides are much simpler, rendering their original characteristics easier to maintain without significant alteration of their structure. On the other hand, proteins tend to deform due to their susceptibility to environmental changes. Combining such superb dielectric properties with their relatively stable nature, peptides could be utilized as a component of electronic devices ranging from basic capacitors to more complex thin-film transistors. In this paper, a peptide chain (YYACAYY) composed of tyrosine, alanine, and cysteine was extensively studied using an impedance analyzer to determine its innate charge movement mechanism in order to extend our understanding of the electric properties of peptides. The movement of mobile protons inside the peptide insulator was found to be the source of the high relative permittivity of the peptide insulator, and the dielectric constant of the peptide insulator was found to be over 17 in humid conditions. By widening the understanding of the dielectric properties of the peptide insulator, it is expected that the peptide can be further utilized as an insulator in various electronic devices.

| S-EPMC9086689 | biostudies-literature

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