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International Journal of Molecular... Mar 2023Voltage-gated ion channels are integral membrane proteins that respond to changes in membrane potential with rapid variations in membrane permeability to ions [...].
Voltage-gated ion channels are integral membrane proteins that respond to changes in membrane potential with rapid variations in membrane permeability to ions [...].
Topics: Ion Channels; Membrane Potentials; Cell Membrane Permeability; Ions; Drug Design
PubMed: 37047455
DOI: 10.3390/ijms24076484 -
Accounts of Chemical Research Jan 2020Membrane potential is a fundamental biophysical property maintained by every cell on earth. In specialized cells like neurons, rapid changes in membrane potential drive... (Review)
Review
Membrane potential is a fundamental biophysical property maintained by every cell on earth. In specialized cells like neurons, rapid changes in membrane potential drive the release of chemical neurotransmitters. Coordinated, rapid changes in neuronal membrane potential across large numbers of interconnected neurons form the basis for all of human cognition, sensory perception, and memory. Despite the importance of this highly orchestrated and distributed activity, the traditional method for recording membrane potential is through the use of highly invasive single-cell electrodes that offer only a small glimpse of the total activity within a system. Fluorescent dyes that change their optical properties in response to changes in biological voltage have the potential to provide a powerful complement to traditional electrode-based methods of inquiry. Voltage-sensitive fluorescent indicators would allow the direct observation of membrane potential changes, significantly expanding our ability to monitor membrane potential dynamics in living systems. Toward this end, we have initiated a program to design, synthesize, and apply voltage-sensitive fluorophores that report on membrane potential dynamics with high sensitivity and speed. The basis for this optical voltage sensing is membrane potential-dependent photoinduced electron transfer (PeT). Voltage-sensitive fluorophores, or VoltageFluors, possess a fluorophore, a conjugated molecular wire, and an aniline donor. At resting potentials, in which the cell has a hyperpolarized or negative potential relative to the outside of the cell, PeT from the aniline donor is enhanced and fluorescence is diminished. At depolarized potentials, the membrane potential decreases the rate of PeT, allowing an increase in fluorescence. We show that a number of different fluorophores, molecular wires, and aniline donors can be employed to generate fast and sensitive VoltageFluor dyes. Multiple lines of evidence point to a PeT-based mechanism for voltage sensing, delivering fast response kinetics (∼25 ns), good sensitivity (>60% Δ/), compatibility with two-photon illumination, excellent signal-to-noise, and the ability to detect neuronal and cardiac action potentials in single trials. In this Account, we provide an overview of the challenges facing the design of fluorescent voltage indicators. We trace the development of molecular wire-based fluorescent voltage indicators within our group, beginning from fluorescein-based VoltageFluor to long-wavelength indicators that use modern fluorophores like silicon rhodamine and carbofluorescein. We examine design principles for PeT-based voltage indicators, showcase the use of our recent indicators for two-photon voltage imaging in intact brains, and explore the development of hybrid indicators that can localize to genetically defined cells. Finally, we highlight outstanding challenges to and opportunities for voltage imaging.
Topics: Animals; Fluorescent Dyes; Humans; Membrane Potentials; Molecular Structure
PubMed: 31834772
DOI: 10.1021/acs.accounts.9b00514 -
Methods in Enzymology 2021Membrane potential is a fundamental biophysical parameter common to all of cellular life. Traditional methods to measure membrane potential rely on electrodes, which are...
Membrane potential is a fundamental biophysical parameter common to all of cellular life. Traditional methods to measure membrane potential rely on electrodes, which are invasive and low-throughput. Optical methods to measure membrane potential are attractive because they have the potential to be less invasive and higher throughput than classic electrode based techniques. However, most optical measurements rely on changes in fluorescence intensity to detect changes in membrane potential. In this chapter, we discuss the use of fluorescence lifetime imaging microscopy (FLIM) and voltage-sensitive fluorophores (VoltageFluors, or VF dyes) to estimate the millivolt value of membrane potentials in living cells. We discuss theory, application, protocols, and shortcomings of this approach.
Topics: Fluorescent Dyes; Membrane Potentials; Microscopy, Fluorescence; Optical Imaging
PubMed: 34099175
DOI: 10.1016/bs.mie.2021.02.009 -
Neuroscience Research Jul 2020The plasma membrane of some neurons has an intrinsic electrical property for responding to inputs with a specific frequency. This band-pass property is called the... (Review)
Review
The plasma membrane of some neurons has an intrinsic electrical property for responding to inputs with a specific frequency. This band-pass property is called the resonant behaviour or resonant property, and is thought to be the basis for the frequency response of neurons. Resonance is mediated by a capacitor and resister inherent to the plasma membrane, while ion channels act as phenomenological inductors. A variety of ion channels have been proposed as candidates, such as hyperpolarization-activated cyclic nucleotide-gated potassium (HCN) channels, persistent sodium channels (I), T-type voltage-dependent Ca channels, and M-type K channels. Individual ion channels have unique frequency characteristics and membrane potential dependency. In many neurons, coordinated interactions of two or more ion channels are crucial for generation of resonance. In this review, lines of experimental evidence on ion channel contribution to resonance in rodent brain are summarized.
Topics: Animals; Ion Channels; Membrane Potentials; Neurons; Rodentia; Sodium Channels
PubMed: 31870695
DOI: 10.1016/j.neures.2019.12.013 -
Communications Biology Jul 2022Mitochondrial ultrastructure represents a pinnacle of form and function, with the inner mitochondrial membrane (IMM) forming isolated pockets of cristae membrane (CM),...
Mitochondrial ultrastructure represents a pinnacle of form and function, with the inner mitochondrial membrane (IMM) forming isolated pockets of cristae membrane (CM), separated from the inner-boundary membrane (IBM) by cristae junctions (CJ). Applying structured illumination and electron microscopy, a novel and fundamental function of MICU1 in mediating Ca control over spatial membrane potential gradients (SMPGs) between CM and IMS was identified. We unveiled alterations of SMPGs by transient CJ openings when Ca binds to MICU1 resulting in spatial cristae depolarization. This Ca/MICU1-mediated plasticity of the CJ further provides the mechanistic bedrock of the biphasic mitochondrial Ca uptake kinetics via the mitochondrial Ca uniporter (MCU) during intracellular Ca release: Initially, high Ca opens CJ via Ca/MICU1 and allows instant Ca uptake across the CM through constantly active MCU. Second, MCU disseminates into the IBM, thus establishing Ca uptake across the IBM that circumvents the CM. Under the condition of MICU1 methylation by PRMT1 in aging or cancer, UCP2 that binds to methylated MICU1 destabilizes CJ, disrupts SMPGs, and facilitates fast Ca uptake via the CM.
Topics: Biological Transport; Membrane Potentials; Mitochondria; Mitochondrial Membranes
PubMed: 35778442
DOI: 10.1038/s42003-022-03606-3 -
Channels (Austin, Tex.) Dec 2023Inward rectifier potassium channels (Kir channels) exist in a variety of cells and are involved in maintaining resting membrane potential and signal transduction in most... (Review)
Review
Inward rectifier potassium channels (Kir channels) exist in a variety of cells and are involved in maintaining resting membrane potential and signal transduction in most cells, as well as connecting metabolism and membrane excitability of body cells. It is closely related to normal physiological functions of body and the occurrence and development of some diseases. Although the functional expression of Kir channels and their role in disease have been studied, they have not been fully elucidated. In this paper, the functional expression of Kir channels in vascular endothelial cells and smooth muscle cells and their changes in disease states were reviewed, especially the recent research progress of Kir channels in stem cells was introduced, in order to have a deeper understanding of Kir channels in vascular tissues and provide new ideas and directions for the treatment of related ion channel diseases.
Topics: Endothelial Cells; Potassium Channels, Inwardly Rectifying; Membrane Potentials; Cell Membrane; Myocytes, Smooth Muscle; Potassium
PubMed: 37463317
DOI: 10.1080/19336950.2023.2237303 -
Neurology India 2020Microvessel constriction plays an important role in delayed cerebral ischemia after aneurismal subarachnoid hemorrhage (SAH). This constriction has been demonstrated in...
OBJECTIVES
Microvessel constriction plays an important role in delayed cerebral ischemia after aneurismal subarachnoid hemorrhage (SAH). This constriction has been demonstrated in both animal model and clinical operation. The present study examined the time-related membrane potential (Em) alteration of arterioles isolated from SAH model rats and the correlation between the potential alteration of arterioles and the diameter of basilar artery.
MATERIALS AND METHODS
Sprague-Dawley rats (n = 90), weighing 300 g to 350 g, were divided into t control, sham, and SAH groups. In the SAH group, blood was injected into the prechiasmatic cistern of the rats. The Em of arterioles and basilar artery diameter was measured using whole-cell clamp recordings and pressure myograph, respectively, 1, 3, 5, 7, and 14 days after SAH. The correlation was evaluated using Pearson correlation coefficients.
RESULTS
The Em of arterioles in the SAH group depolarized on days 3, 5, and 7, and peaked on day 7. The diameters significantly decreased on days 1, 3, 5, 7, and 14, and the smallest diameter was observed on day 7. A significant correlation between potential alteration of arterioles and diameter of basilar artery was found.
CONCLUSIONS
Similar to the artery, arteriole constriction is also involved in the pathophysiological events of delayed cerebral ischemia.
Topics: Animals; Arterioles; Basilar Artery; Disease Models, Animal; Membrane Potentials; Muscle, Smooth, Vascular; Patch-Clamp Techniques; Rats; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 32189713
DOI: 10.4103/0028-3886.280652 -
Bioelectrochemistry (Amsterdam,... Dec 2020Conventional electric stimuli of micro- and millisecond duration excite or activate cells at voltages 10-100 times below the electroporation threshold. This ratio is... (Review)
Review
Conventional electric stimuli of micro- and millisecond duration excite or activate cells at voltages 10-100 times below the electroporation threshold. This ratio is remarkably different for nanosecond electric pulses (nsEP), which caused excitation and activation only at or above the electroporation threshold in diverse cell lines, primary cardiomyocytes, neurons, and chromaffin cells. Depolarization to the excitation threshold often results from (or is assisted by) the loss of the resting membrane potential due to ion leaks across the membrane permeabilized by nsEP. Slow membrane resealing and the build-up of electroporation damages prevent repetitive excitation by nsEP. However, peripheral nerves and muscles are exempt from this rule and withstand multiple cycles of excitation by nsEP without the loss of function or signs of electroporation. We show that the damage-free excitation by nsEP may be enabled by the membrane charging time constant sufficiently large to (1) cap the peak transmembrane voltage during nsEP below the electroporation threshold, and (2) extend the post-nsEP depolarization long enough to activate voltage-gated ion channels. The low excitatory efficacy of nsEP compared to longer pulses makes them advantageous for medical applications where the neuromuscular excitation is an unwanted side effect, such as electroporation-based cancer and tissue ablation.
Topics: Animals; Cell Line; Cell Membrane Permeability; Electric Stimulation; Electroporation; Humans; Membrane Potentials
PubMed: 32711366
DOI: 10.1016/j.bioelechem.2020.107598 -
The Science of the Total Environment Apr 2020Biochar-based compound fertilizers (BCF) and amendments have proven to enhance crop yields and modify soil properties (pH, nutrients, organic matter, structure etc.) and...
Biochar-based compound fertilizers (BCF) and amendments have proven to enhance crop yields and modify soil properties (pH, nutrients, organic matter, structure etc.) and are now in commercial production in China. While there is a good understanding of the changes in soil properties following biochar addition, the interactions within the rhizosphere remain largely unstudied, with benefits to yield observed beyond the changes in soil properties alone. We investigated the rhizosphere interactions following the addition of an activated wheat straw BCF at an application rates of 0.25% (g·g soil), which could potentially explain the increase of plant biomass (by 67%), herbage N (by 40%) and P (by 46%) uptake in the rice plants grown in the BCF-treated soil, compared to the rice plants grown in the soil with conventional fertilizer alone. Examination of the roots revealed that micron and submicron-sized biochar were embedded in the plaque layer. BCF increased soil Eh by 85 mV and increased the potential difference between the rhizosphere soil and the root membrane by 65 mV. This increased potential difference lowered the free energy required for root nutrient accumulation, potentially explaining greater plant nutrient content and biomass. We also demonstrate an increased abundance of plant-growth promoting bacteria and fungi in the rhizosphere. We suggest that the redox properties of the biochar cause major changes in electron status of rhizosphere soils that drive the observed agronomic benefits.
Topics: Biomass; Charcoal; China; Fertilizers; Membrane Potentials; Oryza; Soil
PubMed: 31958720
DOI: 10.1016/j.scitotenv.2019.136431 -
Physiological Reports Jan 2023The purpose of this study was to determine how sensory neurons respond to high-frequency membrane potential alternation between depolarization and hyperpolarization....
The purpose of this study was to determine how sensory neurons respond to high-frequency membrane potential alternation between depolarization and hyperpolarization. Membrane currents were recorded from dissociated dorsal root ganglion (DRG) neurons of adult rats using the whole cell patch clamp technique in voltage clamp mode. Stepwise depolarization of the membrane was applied first to determine the threshold membrane potential for inducing an action potential (AP) current. Then, membrane potential alternation between depolarization (to +20 mV) and hyperpolarization (to -110 mV) was applied to the neuron for 10 s at different frequencies (10 Hz to 1 kHz). The tested DRG neurons had APs of either a long duration (>10 ms) or a short duration (<10 ms). Membrane potential alternation at ≥500 Hz completely disrupted the AP generation, disabled the ion channel gating function, and produced membrane current alternating symmetrically across zero. Replacing extracellular sodium with potassium increased the amplitude of the membrane current response and caused the membrane current to be larger during hyperpolarization than during depolarization. These results support the hypothesis that high-frequency biphasic stimulation blocks axonal conduction by driving the potassium channel open constantly. Understanding neural membrane response to high-frequency membrane potential alternation is important to reveal the possible mechanisms underlying axonal conduction block induced by high-frequency biphasic stimulation.
Topics: Rats; Animals; Membrane Potentials; Ganglia, Spinal; Neurons; Action Potentials; Neurons, Afferent
PubMed: 36695759
DOI: 10.14814/phy2.15582