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Current Opinion in Pharmacology Feb 2022Ligand-gated ion channels (LGIC, also referred to as ionotropic receptors) are important transmembrane proteins that open to allow ions to flow across the membrane and... (Review)
Review
Ligand-gated ion channels (LGIC, also referred to as ionotropic receptors) are important transmembrane proteins that open to allow ions to flow across the membrane and locally modify the membrane potential in response to the binding of a ligand. For more than a decade, a tremendous effort has been carried out in the determination of many LGIC structures in high resolution, leading to an unprecedented molecular description of channel gating. However, it is sometimes difficult to classify experimentally derived structures to their corresponding functional states, and alternative methods may help resolve or refine this issue. In this review, we focus on the application of photo-isomerizable tweezers (PIT) as a powerful strategy to interrogate molecular mechanisms of LGIC while assessing their functionality by electrophysiology.
Topics: Humans; Ligands; Membrane Potentials
PubMed: 34965483
DOI: 10.1016/j.coph.2021.11.011 -
International Journal of Molecular... Jul 2023Sperm cells must undergo a complex maturation process after ejaculation to be able to fertilize an egg. One component of this maturation is hyperpolarization of the... (Review)
Review
Sperm cells must undergo a complex maturation process after ejaculation to be able to fertilize an egg. One component of this maturation is hyperpolarization of the membrane potential to a more negative value. The ion channel responsible for this hyperpolarization, SLO3, was first cloned in 1998, and since then much progress has been made to determine how the channel is regulated and how its function intertwines with various signaling pathways involved in sperm maturation. Although was originally thought to be present only in the sperm of mammals, recent evidence suggests that a primordial form of the gene is more widely expressed in some fish species. , like many reproductive genes, is rapidly evolving with low conservation between closely related species and different regulatory and pharmacological profiles. Despite these differences, SLO3 appears to have a conserved role in regulating sperm membrane potential and driving large changes in response to stimuli. The effect of this hyperpolarization of the membrane potential may vary among mammalian species just as the regulation of the channel does. Recent discoveries have elucidated the role of SLO3 in these processes in human sperm and provided tools to target the channel to affect human fertility.
Topics: Animals; Male; Humans; Membrane Potentials; Large-Conductance Calcium-Activated Potassium Channels; Semen; Spermatozoa; Signal Transduction; Mammals
PubMed: 37446382
DOI: 10.3390/ijms241311205 -
Advanced Science (Weinheim,... Mar 2023Recent studies have shown that bacterial membrane potential is dynamic and plays signaling roles. Yet, little is still known about the mechanisms of membrane potential...
Recent studies have shown that bacterial membrane potential is dynamic and plays signaling roles. Yet, little is still known about the mechanisms of membrane potential dynamics regulation-owing to a scarcity of appropriate research tools. Optical modulation of bacterial membrane potential could fill this gap and provide a new approach for studying and controlling bacterial physiology and electrical signaling. Here, the authors show that a membrane-targeted azobenzene (Ziapin2) can be used to photo-modulate the membrane potential in cells of the Gram-positive bacterium Bacillus subtilis. It is found that upon exposure to blue-green light (λ = 470 nm), isomerization of Ziapin2 in the bacteria membrane induces hyperpolarization of the potential. To investigate the origin of this phenomenon, ion-channel-deletion strains and ion channel blockers are examined. The authors found that in presence of the chloride channel blocker idanyloxyacetic acid-94 (IAA-94) or in absence of KtrAB potassium transporter, the hyperpolarization response is attenuated. These results reveal that the Ziapin2 isomerization can induce ion channel opening in the bacterial membrane and suggest that Ziapin2 can be used for studying and controlling bacterial electrical signaling. This new optical tool could contribute to better understand various microbial phenomena, such as biofilm electric signaling and antimicrobial resistance.
Topics: Membrane Potentials; Azo Compounds; Potassium; Bacteria
PubMed: 36710255
DOI: 10.1002/advs.202205007 -
Advances in Experimental Medicine and... 2020Imaging techniques may overcome the limitations of electrode techniques to measure locally not only membrane potential changes, but also ionic currents. Here, we review... (Review)
Review
Imaging techniques may overcome the limitations of electrode techniques to measure locally not only membrane potential changes, but also ionic currents. Here, we review a recently developed approach to image native neuronal Ca currents from brain slices. The technique is based on combined fluorescence recordings using low-affinity Ca indicators possibly in combination with voltage sensitive dyes. We illustrate how the kinetics of a Ca current can be estimated from the Ca fluorescence change and locally correlated with the change of membrane potential, calibrated on an absolute scale, from the voltage fluorescence change. We show some representative measurements from the dendrites of CA1 hippocampal pyramidal neurons, from olfactory bulb mitral cells and from cerebellar Purkinje neurons. We discuss the striking difference in data analysis and interpretation between Ca current measurements obtained using classical electrode techniques and the physiological currents obtained using this novel approach. Finally, we show how important is the kinetic information on the native Ca current to explore the potential molecular targets of the Ca flux from each individual Ca channel.
Topics: Animals; Calcium; Calcium Channels; Dendrites; Humans; Membrane Potentials; Neuroimaging; Optical Imaging; Pyramidal Cells
PubMed: 31646507
DOI: 10.1007/978-3-030-12457-1_4 -
Clinical Neurophysiology : Official... Jul 2023To understand the pathophysiology of myopathies by using muscle velocity recovery cycles (MVRC) and frequency ramp (RAMP) methodologies.
OBJECTIVE
To understand the pathophysiology of myopathies by using muscle velocity recovery cycles (MVRC) and frequency ramp (RAMP) methodologies.
METHODS
42 patients with quantitative electromyography (qEMG) and biopsy or genetic verified myopathy and 42 healthy controls were examined with qEMG, MVRC and RAMP, all recorded from the anterior tibial muscle.
RESULTS
There were significant differences in the motor unit potential (MUP) duration, the early and late supernormalities of the MVRC and the RAMP latencies in myopathy patients compared to controls (p < 0.05 apart from muscle relatively refractory period (MRRP)). When dividing into subgroups, the above-mentioned changes in MVRC and RAMP parameters were increased for the patients with non-inflammatory myopathy, while there were no significant changes in the group of patients with inflammatory myopathy.
CONCLUSIONS
The MVRC and RAMP parameters can discriminate between healthy controls and myopathy patients, more significantly for non-inflammatory myopathy. MVRC differences with normal MRRP in myopathy differs from other conditions with membrane depolarisation.
SIGNIFICANCE
MVCR and RAMP may have a potential in understanding disease pathophysiology in myopathies. The pathogenesis in non-inflammatory myopathy does not seem to be caused by a depolarisation of the resting membrane potential but rather by the change in sodium channels of the muscle membrane.
Topics: Humans; Muscle, Skeletal; Electromyography; Membrane Potentials; Muscular Diseases; Muscle Contraction
PubMed: 37148747
DOI: 10.1016/j.clinph.2023.04.001 -
Physics of Life Reviews Dec 2022In recent decades, medical research has been primarily focused on the inherited aspect of cancers, despite the reality that only 5-10% of tumours discovered are derived... (Review)
Review
In recent decades, medical research has been primarily focused on the inherited aspect of cancers, despite the reality that only 5-10% of tumours discovered are derived from genetic causes. Cancer is a broad term, and therefore it is inaccurate to address it as a purely genetic disease. Understanding cancer cells' behaviour is the first step in countering them. Behind the scenes, there is a complicated network of environmental factors, DNA errors, metabolic shifts, and electrostatic alterations that build over time and lead to the illness's development. This latter aspect has been analyzed in previous studies, but how the different electrical changes integrate and affect each other is rarely examined. Every cell in the human body possesses electrical properties that are essential for proper behaviour both within and outside of the cell itself. It is not yet clear whether these changes correlate with cell mutation in cancer cells, or only with their subsequent development. Either way, these aspects merit further investigation, especially with regards to their causes and consequences. Trying to block changes at various levels of occurrence or assisting in their prevention could be the key to stopping cells from becoming cancerous. Therefore, a comprehensive understanding of the current knowledge regarding the electrical landscape of cells is much needed. We review four essential electrical characteristics of cells, providing a deep understanding of the electrostatic changes in cancer cells compared to their normal counterparts. In particular, we provide an overview of intracellular and extracellular pH modifications, differences in ionic concentrations in the cytoplasm, transmembrane potential variations, and changes within mitochondria. New therapies targeting or exploiting the electrical properties of cells are developed and tested every year, such as pH-dependent carriers and tumour-treating fields. A brief section regarding the state-of-the-art of these therapies can be found at the end of this review. Finally, we highlight how these alterations integrate and potentially yield indications of cells' malignancy or metastatic index.
Topics: Humans; Membrane Potentials; Neoplasms; Mitochondria
PubMed: 36265200
DOI: 10.1016/j.plrev.2022.09.003 -
American Journal of Physiology. Cell... Jun 2022We endeavored to understand the factors determining the peak force-resting membrane potential () relationships of isolated slow-twitch soleus and fast-twitch extensor...
We endeavored to understand the factors determining the peak force-resting membrane potential () relationships of isolated slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles from mice (25°C), especially in relation to fatigue. Interrelationships between intracellular K activity ([Formula: see text]), extracellular K concentration ([K]), resting , action potentials, and force were studied. The large resting variation was mainly due to the variability of [Formula: see text]. Action potential overshoot-resting relationships determined at 4 and 8-10 mM [K] after short (<5 min) and prolonged (>50 min) depolarization periods revealed a constant overshoot from -90 to -70 mV providing a safety margin. Overshoot decline with depolarization beyond -70 mV was less after short than prolonged depolarization. Inexcitable fibers occurred only with prolonged depolarization. The overshoot decline during action potential trains (2 s) exceeded that during short depolarizations. Concomitant lower extracellular [Na] and raised [K] depressed the overshoot in an additive manner and peak force in a synergistic manner. Raised [K]-induced force loss was exacerbated with transverse wire versus parallel plate stimulation in soleus, implicating action potential propagation failure in the surface membrane. Increasing stimulus pulse parameters restored tetanic force at 9-10 mM [K] in soleus but not EDL, indicative of action potential failure within trains. The peak tetanic force-resting relationships (determined with resting from deeper rather than surface fibers) were dynamic and showed pronounced force depression over -69 to -60 mV in both muscle types, implicating that such depolarization contributes to fatigue. The K-Na interaction shifted this relationship toward less depolarized potentials, suggesting that the combined ionic effect is physiologically important during fatigue.
Topics: Animals; Fatigue; Membrane Potentials; Mice; Muscle Contraction; Muscle Fatigue; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Potassium; Sodium
PubMed: 35385328
DOI: 10.1152/ajpcell.00401.2021 -
ACS Nano Mar 2020The interfacing of nanoparticle (NP) materials with cells, tissues, and organisms for a range of applications including imaging, sensing, and drug delivery continues at... (Review)
Review
The interfacing of nanoparticle (NP) materials with cells, tissues, and organisms for a range of applications including imaging, sensing, and drug delivery continues at a rampant pace. An emerging theme in this area is the use of NPs and nanostructured surfaces for the imaging and/or control of cellular membrane potential (MP). Given the important role that MP plays in cellular biology, both in normal physiology and in disease, new materials and methods are continually being developed to probe the activity of electrically excitable cells such as neurons and muscle cells. In this Review, we highlight the current state of the art for both the visualization and control of MP using traditional materials and techniques, discuss the advantageous features of NPs for performing these functions, and present recent examples from the literature of how NP materials have been implemented for the visualization and control of the activity of electrically excitable cells. We conclude with a forward-looking perspective of how we expect to see this field progress in the near term and further into the future.
Topics: Cell Membrane; Humans; Membrane Potentials; Muscles; Nanoparticles; Neurons
PubMed: 32078291
DOI: 10.1021/acsnano.9b10163 -
Journal of Neurophysiology Dec 2023In recent years, several studies have shown a respiratory drive of the local field potential (LFP) in numerous brain areas so that the respiratory rhythm could be...
In recent years, several studies have shown a respiratory drive of the local field potential (LFP) in numerous brain areas so that the respiratory rhythm could be considered as a master clock promoting communication between distant brain locations. However, outside of the olfactory system, it remains unknown whether the respiratory rhythm could shape membrane potential (MP) oscillations. To fill this gap, we co-recorded MP and LFP activities in different nonolfactory brain areas, medial prefrontal cortex (mPFC), primary somatosensory cortex (S1), primary visual cortex (V1), and hippocampus (HPC), in urethane-anesthetized rats. Using respiratory cycle-by-cycle analysis, we observed that respiration could modulate both MP and spiking discharges in all recorded areas during episodes that we called respiration-related oscillations (RRo). Further quantifications revealed that RRo episodes were transient in most neurons (5 consecutive respiratory cycles in average). RRo development in MP was largely correlated with the presence of respiratory modulation in the LFP. By showing that the respiratory rhythm influenced brain activities deep to the MP of nonolfactory neurons, our data support the idea that respiratory rhythm could mediate long-range communication between brain areas. In this study, we evidenced strong respiratory-driven oscillations of neuronal membrane potential and spiking discharge in various nonolfactory areas of the mammal brain. These oscillations were found in the medial prefrontal cortex, primary somatosensory cortex, primary visual cortex, and hippocampus. These findings support the idea that respiratory rhythm could be used as a common clock to set the dynamics of large-scale neuronal networks on the same slow rhythm.
Topics: Rats; Animals; Membrane Potentials; Respiration; Hippocampus; Respiratory Rate; Neurons; Theta Rhythm; Mammals
PubMed: 37964739
DOI: 10.1152/jn.00487.2022 -
Biochemistry. Biokhimiia Oct 2023An overview of current notions on the mechanism of generation of a transmembrane electric potential difference (Δψ) during the catalytic cycle of a bd-type triheme... (Review)
Review
An overview of current notions on the mechanism of generation of a transmembrane electric potential difference (Δψ) during the catalytic cycle of a bd-type triheme terminal quinol oxidase is presented in this work. It is suggested that the main contribution to Δψ formation is made by the movement of H+ across the membrane along the intra-protein hydrophilic proton-conducting pathway from the cytoplasm to the active site for oxygen reduction of this bacterial enzyme.
Topics: Membrane Potentials; Cytochrome b Group; Escherichia coli Proteins; Electron Transport Chain Complex Proteins; Cytochromes; Oxidation-Reduction
PubMed: 38105020
DOI: 10.1134/S0006297923100073