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1.
Sci Rep ; 14(1): 6031, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472404

RESUMO

The dysfunction of ion channels is a causative factor in a variety of neurological diseases, thereby defining the implicated channels as key drug targets. The detection of functional changes in multiple specific ionic currents currently presents a challenge, particularly when the neurological causes are either a priori unknown, or are unexpected. Traditional patch clamp electrophysiology is a powerful tool in this regard but is low throughput. Here, we introduce a single-shot method for detecting alterations amongst a range of ion channel types from subtle changes in membrane voltage in response to a short chaotically driven current clamp protocol. We used data assimilation to estimate the parameters of individual ion channels and from these we reconstructed ionic currents which exhibit significantly lower error than the parameter estimates. Such reconstructed currents thereby become sensitive predictors of functional alterations in biological ion channels. The technique correctly predicted which ionic current was altered, and by approximately how much, following pharmacological blockade of BK, SK, A-type K+ and HCN channels in hippocampal CA1 neurons. We anticipate this assay technique could aid in the detection of functional changes in specific ionic currents during drug screening, as well as in research targeting ion channel dysfunction.


Assuntos
Canais Iônicos , Neurônios , Eletrofisiologia , Canais Iônicos/metabolismo , Neurônios/metabolismo , Membrana Celular/metabolismo , Transporte de Íons
2.
STAR Protoc ; 5(1): 102909, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38427565

RESUMO

Here, we present a protocol for the fabrication of transparent implantable electrode arrays for integrating optogenetics and electrophysiology. We describe steps for fabricating microelectrodes using the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate). We then detail procedures for analyzing performance of the electrodes and recording light-evoked neural activities from the transgenic mouse. This protocol utilizes photolithography rather than conventional electrodeposition. For complete details on the use and execution of this protocol, please refer to Cho et al. (2022).1.


Assuntos
Optogenética , Roedores , Camundongos , Animais , Microeletrodos , Eletrodos Implantados , Camundongos Transgênicos , Eletrofisiologia/métodos
3.
PLoS One ; 19(3): e0298320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38483943

RESUMO

BACKGROUND: Deep Brain Stimulation (DBS), applying chronic electrical stimulation of subcortical structures, is a clinical intervention applied in major neurologic disorders. In order to achieve a good clinical effect, accurate electrode placement is necessary. The primary localisation is typically based on presurgical MRI imaging, often followed by intra-operative electrophysiology recording to increase the accuracy and to compensate for brain shift, especially in cases where the surgical target is small, and there is low contrast: e.g., in Parkinson's disease (PD) and in its common target, the subthalamic nucleus (STN). METHODS: We propose a novel, fully automatic method for intra-operative surgical navigation. First, the surgical target is segmented in presurgical MRI images using a statistical shape-intensity model. Next, automated alignment with intra-operatively recorded microelectrode recordings is performed using a probabilistic model of STN electrophysiology. We apply the method to a dataset of 120 PD patients with clinical T2 1.5T images, of which 48 also had available microelectrode recordings (MER). RESULTS: The proposed segmentation method achieved STN segmentation accuracy around dice = 0.60 compared to manual segmentation. This is comparable to the state-of-the-art on low-resolution clinical MRI data. When combined with electrophysiology-based alignment, we achieved an accuracy of 0.85 for correctly including recording sites of STN-labelled MERs in the final STN volume. CONCLUSION: The proposed method combines image-based segmentation of the subthalamic nucleus with microelectrode recordings to estimate their mutual location during the surgery in a fully automated process. Apart from its potential use in clinical targeting, the method can be used to map electrophysiological properties to specific parts of the basal ganglia structures and their vicinity.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/cirurgia , Estimulação Encefálica Profunda/métodos , Imageamento por Ressonância Magnética , Microeletrodos , Eletrofisiologia
4.
J Neurosci ; 44(11)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38479812

RESUMO

The axon is a neuronal structure capable of processing, encoding, and transmitting information. This assessment contrasts with a limiting, but deeply rooted, perspective where the axon functions solely as a transmission cable of somatodendritic activity, sending signals in the form of stereotypical action potentials. This perspective arose, at least partially, because of the technical difficulties in probing axons: their extreme length-to-diameter ratio and intricate growth paths preclude the study of their dynamics through traditional techniques. Recent findings are challenging this view and revealing a much larger repertoire of axonal computations. Axons display complex signaling processes and structure-function relationships, which can be modulated via diverse activity-dependent mechanisms. Additionally, axons can exhibit patterns of activity that are dramatically different from those of their corresponding soma. Not surprisingly, many of these recent discoveries have been driven by novel technology developments, which allow for in vitro axon electrophysiology with unprecedented spatiotemporal resolution and signal-to-noise ratio. In this review, we outline the state-of-the-art in vitro toolset for axonal electrophysiology and summarize the recent discoveries in axon function it has enabled. We also review the increasing repertoire of microtechnologies for controlling axon guidance which, in combination with the available cutting-edge electrophysiology and imaging approaches, have the potential for more controlled and high-throughput in vitro studies. We anticipate that a larger adoption of these new technologies by the neuroscience community will drive a new era of experimental opportunities in the study of axon physiology and consequently, neuronal function.


Assuntos
Axônios , Neurônios , Axônios/fisiologia , Potenciais de Ação/fisiologia , Fenômenos Eletrofisiológicos , Eletrofisiologia
5.
Commun Biol ; 7(1): 193, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365955

RESUMO

REM sleep is critical for memory, emotion, and cognition. Manipulating brain activity during REM could improve our understanding of its function and benefits. Earlier studies have suggested that auditory stimulation in REM might modulate REM time and reduce rapid eye movement density. Building on this, we studied the cognitive effects and electroencephalographic responses related to such stimulation. We used acoustic stimulation locked to eye movements during REM and compared two overnight conditions (stimulation and no-stimulation). We evaluated the impact of this stimulation on REM sleep duration and electrophysiology, as well as two REM-sensitive memory tasks: visual discrimination and mirror tracing. Our results show that this auditory stimulation in REM decreases the rapid eye movements that characterize REM sleep and improves performance on the visual task but is detrimental to the mirror tracing task. We also observed increased beta-band activity and decreased theta-band activity following stimulation. Interestingly, these spectral changes were associated with changes in behavioural performance. These results show that acoustic stimulation can modulate REM sleep and suggest that different memory processes underpin its divergent impacts on cognitive performance.


Assuntos
Eletroencefalografia , Sono REM , Sono REM/fisiologia , Estimulação Acústica , Cognição , Eletrofisiologia
6.
CNS Neurosci Ther ; 30(2): e14571, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38421092

RESUMO

BACKGROUND: In α-synucleinopathies, the dysfunction of the autonomic nervous system which typically manifests as orthostatic hypotension (OH) often leads to severe consequences and poses therapeutic challenges. This study aims to discover the brain-cardiac electrophysiological changes in OH patients with α-synucleinopathies using the rapid quantitative electroencephalography (qEEG) coupled with heart rate variability (HRV) technique to identify rapid, noninvasive biomarkers for early warning and diagnosis, as well as shed new light on complementary treatment approaches such as brain stimulation targets. METHODS: In this study, 26 subjects of α-synucleinopathies with OH (α-OH group), 21 subjects of α-synucleinopathies without OH (α-NOH group), and 34 healthy controls (control group) were included from September 2021 to August 2023 (NCT05527067). The heart rate-blood pressure variations in supine and standing positions were monitored, and synchronization parameters of seated resting-state HRV coupled with qEEG were collected. Time-domain and frequency-domain of HRV measures as well as peak frequency and power of the brainwaves were extracted. Differences between these three groups were compared, and correlations between brain-heart parameters were analyzed. RESULTS: The research results showed that the time-domain parameters such as MxDMn, pNN50, RMSSD, and SDSD of seated resting-state HRV exhibited a significant decrease only in the α-OH group compared to the healthy control group (p < 0.05), while there was no significant difference between the α-NOH group and the healthy control group. Several time-domain and frequency-domain parameters of seated resting-state HRV were found to be correlated with the blood pressure changes within the first 5 min of transitioning from supine to standing position (p < 0.05). Differences were observed in the power of beta1 waves (F4 and Fp2) and beta2 waves (Fp2 and F4) in the seated resting-state qEEG between the α-OH and α-NOH groups (p < 0.05). The peak frequency of theta waves in the Cz region also showed a difference (p < 0.05). The power of beta2 waves in the Fp2 and F4 brain regions correlated with frequency-domain parameters of HRV (p < 0.05). Additionally, abnormal electrical activity in the alpha, theta, and beta1 waves was associated with changes in heart rate and blood pressure within the first 5 min of transitioning from supine to standing position (p < 0.05). CONCLUSION: Rapid resting-state HRV with certain time-domain parameters below normal levels may serve as a predictive indicator for the occurrence of orthostatic hypotension (OH) in patients with α-synucleinopathies. Additionally, the deterioration of HRV parameters correlates with synchronous abnormal qEEG patterns, which can provide insights into the brain stimulation target areas for OH in α-synucleinopathy patients.


Assuntos
Hipotensão Ortostática , Sinucleinopatias , Humanos , Hipotensão Ortostática/diagnóstico , Hipotensão Ortostática/terapia , Frequência Cardíaca/fisiologia , Encéfalo/diagnóstico por imagem , Pressão Sanguínea/fisiologia , Eletroencefalografia , Eletrofisiologia
7.
Int J Cardiol ; 401: 131817, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38307422

RESUMO

BACKGROUND: High-altitude exposure changes the electrical conduction of the heart. However, reports on electrocardiogram (ECG) characteristics and potent prophylactic agents during high-altitude acclimatization and de-acclimatization are inadequate. This study aimed to investigate the effects of ubiquinol on electrophysiology after high-altitude hypoxia and reoxygenation. METHODS: The study was a prospective, randomized, double-blind, placebo-controlled trial. Forty-one participants were randomly divided into two groups receiving ubiquinol 200 mg daily or placebo orally 14 days before flying to high altitude (3900 m) until the end of the study. Cardiopulmonary exercise testing was performed at baseline (300 m), on the third day after reaching high altitude, and on the seventh day after returning to baseline. RESULTS: Acute high-altitude exposure prolonged resting ventricular repolarization, represented by increased corrected QT interval (455.9 ± 23.4 vs. 427.1 ± 19.1 ms, P < 0.001) and corrected Tpeak-Tend interval (155.5 ± 27.4 vs. 125.3 ± 21.1 ms, P < 0.001), which recovered after returning to low altitude. Ubiquinol supplementation shortened the hypoxia-induced extended Tpeak-Tend interval (-7.7 ms, [95% confidence interval (CI), -13.8 to -1.6], P = 0.014), Tpeak-Tend /QT interval (-0.014 [95% CI, -0.027 to -0.002], P = 0.028), and reserved maximal heart rate (11.9 bpm [95% CI, 3.2 to 20.6], P = 0.013) during exercise at high altitude. Furthermore, the decreased resting amplitude of the ST-segment in the V3 lead was correlated with decreased peak oxygen pulse (R = 0.713, P < 0.001) and maximum oxygen consumption (R = 0.595, P < 0.001). CONCLUSIONS: Our results illustrated the electrophysiology changes during high-altitude acclimatization and de-acclimatization. Similarly, ubiquinol supplementation shortened the prolonged Tpeak-Tend interval and reserved maximal heart rate during exercise at high altitude. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2200059900.


Assuntos
Altitude , Aptidão Cardiorrespiratória , Ubiquinona/análogos & derivados , Humanos , Estudos Prospectivos , Hipóxia , Aclimatação , Eletrofisiologia
8.
Sci Adv ; 10(8): eadj4399, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38381836

RESUMO

Identifying different sleep stages in humans and other mammals has traditionally relied on electroencephalograms. Such an approach is not feasible in certain animals such as invertebrates, although these animals could also be sleeping in stages. Here, we perform long-term multichannel local field potential recordings in the brains of behaving flies undergoing spontaneous sleep bouts. We acquired consistent spatial recordings of local field potentials across multiple flies, allowing us to compare brain activity across awake and sleep periods. Using machine learning, we uncover distinct temporal stages of sleep and explore the associated spatial and spectral features across the fly brain. Further, we analyze the electrophysiological correlates of microbehaviors associated with certain sleep stages. We confirm the existence of a distinct sleep stage associated with rhythmic proboscis extensions and show that spectral features of this sleep-related behavior differ significantly from those associated with the same behavior during wakefulness, indicating a dissociation between behavior and the brain states wherein these behaviors reside.


Assuntos
Fenômenos Fisiológicos do Sistema Nervoso , Sono , Animais , Humanos , Sono/fisiologia , Fases do Sono/fisiologia , Drosophila/fisiologia , Eletrofisiologia , Mamíferos
10.
J Neurosci Methods ; 404: 110079, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38340901

RESUMO

BACKGROUND: Electrophysiological recording with glass electrodes is one of the best techniques to measure membrane potential dynamics and ionic currents of voltage-gated channels in neurons. However, artifactual variability of the biophysical state variables that determine recording quality can be caused by insufficient affinity between the electrode and cell membrane during the recording. NEW METHOD: We introduce a phospholipid membrane coating on glass electrodes to improve intracellular electrophysiology recording quality. Membrane-coated electrodes were prepared with a tip-dip protocol for perforated-patch, sharp-electrode current-clamp, and cell-attached patch-clamp recordings from specific circadian clock neurons in Drosophila. We perform quantitative comparisons based on the variability of functional biophysical parameters used in various electrophysiological methods, and advanced statistical comparisons based on the degree of stationariness and signal-to-noise ratio. RESULTS: Results indicate a dramatic reduction in artifactual variabilities of functional parameters from enhanced stability. We also identify significant exclusions of a statistically estimated noise component in a time series of membrane voltage signals, improving signal-to-noise ratio. COMPARISON WITH EXISTING METHODS: Compared to standard glass electrodes, using membrane-coated glass electrodes achieves improved recording quality in intracellular electrophysiology. CONCLUSIONS: Electrophysiological recordings from Drosophila central neurons can be technically challenging, however, membrane-coated electrodes will possibly be beneficial for reliable data acquisition and improving the technical feasibility of axonal intracellular activities measurements and single-channel recordings. The improved electrical stability of the recordings should also contribute to increased mechanical stability, thus facilitating long-term stable measurements of neural activity. Therefore, it is possible that membrane-coated electrodes will be useful for any model system.


Assuntos
Drosophila , Neurônios , Animais , Eletrodos , Potenciais da Membrana/fisiologia , Neurônios/fisiologia , Eletrofisiologia
11.
Herzschrittmacherther Elektrophysiol ; 35(Suppl 1): 77-82, 2024 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-38411695

RESUMO

The paper presents the history of hope from 1980-1995 to predict the risk of sudden arrhythmic death using electrophysiologic techniques in individual patients. Even if this prediction seems possible in selected highly risk cohorts, many more patients will die in ventricular arrhythmia without fulfilling the criteria. Ultimately, high risk of sudden cardiac death can be predicted in selected patient groups, but not in the majority of patients at risk. It is a history of dashed hope.


Assuntos
Arritmias Cardíacas , Morte Súbita Cardíaca , Humanos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Morte Súbita Cardíaca/prevenção & controle , Eletrofisiologia
13.
Circulation ; 149(10): e937-e952, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38314551

RESUMO

Disorders of the cardiac rhythm may occur in both the fetus and neonate. Because of the immature myocardium, the hemodynamic consequences of either bradyarrhythmias or tachyarrhythmias may be far more significant than in mature physiological states. Treatment options are limited in the fetus and neonate because of limited vascular access, patient size, and the significant risk/benefit ratio of any intervention. In addition, exposure of the fetus or neonate to either persistent arrhythmias or antiarrhythmic medications may have yet-to-be-determined long-term developmental consequences. This scientific statement discusses the mechanism of arrhythmias, pharmacological treatment options, and distinct aspects of pharmacokinetics for the fetus and neonate. From the available current data, subjects of apparent consistency/consensus are presented, as well as future directions for research in terms of aspects of care for which evidence has not been established.


Assuntos
American Heart Association , Arritmias Cardíacas , Recém-Nascido , Estados Unidos , Criança , Humanos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/tratamento farmacológico , Taquicardia , Feto , Eletrofisiologia
14.
Int J Occup Med Environ Health ; 37(1): 84-97, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38375631

RESUMO

OBJECTIVES: Emotions and stress affect voice production. There are only a few reports in the literature on how changes in the autonomic nervous system affect voice production. The aim of this study was to examine emotions and measure stress reactions during a voice examination procedure, particularly changes in the muscles surrounding the larynx. MATERIAL AND METHODS: The study material included 50 healthy volunteers (26 voice workers - opera singers, 24 control subjects), all without vocal complaints. All subjects had good voice quality in a perceptual assessment. The research procedure consisted of 4 parts: an ear, nose, and throat (ENT)­phoniatric examination, surface electromyography, recording physiological indicators (heart rate and skin resistance) using a wearable wristband, and a psychological profile based on questionnaires. RESULTS: The results of the study demonstrated that there was a relationship between positive and negative emotions and stress reactions related to the voice examination procedure, as well as to the tone of the vocal tract muscles. There were significant correlations between measures describing the intensity of experienced emotions and vocal tract muscle maximum amplitude of the cricothyroid (CT) and sternocleidomastoid (SCM) muscles during phonation and non-phonation tasks. Subjects experiencing eustress (favorable stress response) had increased amplitude of submandibular and CT at rest and phonation. Subjects with high levels of negative emotions, revealed positive correlations with SCMmax during the glissando. The perception of positive and negative emotions caused different responses not only in the vocal tract but also in the vegetative system. Correlations were found between emotions and physiological parameters, most markedly in heart rate variability. A higher incidence of extreme emotions was observed in the professional group. CONCLUSIONS: The activity of the vocal tract muscles depends on the type and intensity of the emotions and stress reactions. The perception of positive and negative emotions causes different responses in the vegetative system and the vocal tract. Int J Occup Med Environ Health. 2024;37(1):84-97.


Assuntos
Canto , Humanos , Fonação/fisiologia , Qualidade da Voz/fisiologia , Eletromiografia , Eletrofisiologia
15.
Nature ; 626(8001): 1066-1072, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326610

RESUMO

Animals can learn about sources of danger while minimizing their own risk by observing how others respond to threats. However, the distinct neural mechanisms by which threats are learned through social observation (known as observational fear learning1-4 (OFL)) to generate behavioural responses specific to such threats remain poorly understood. The dorsomedial prefrontal cortex (dmPFC) performs several key functions that may underlie OFL, including processing of social information and disambiguation of threat cues5-11. Here we show that dmPFC is recruited and required for OFL in mice. Using cellular-resolution microendoscopic calcium imaging, we demonstrate that dmPFC neurons code for observational fear and do so in a manner that is distinct from direct experience. We find that dmPFC neuronal activity predicts upcoming switches between freezing and moving state elicited by threat. By combining neuronal circuit mapping, calcium imaging, electrophysiological recordings and optogenetics, we show that dmPFC projections to the midbrain periaqueductal grey (PAG) constrain observer freezing, and that amygdalar and hippocampal inputs to dmPFC opposingly modulate observer freezing. Together our findings reveal that dmPFC neurons compute a distinct code for observational fear and coordinate long-range neural circuits to select behavioural responses.


Assuntos
Sinais (Psicologia) , Medo , Vias Neurais , Córtex Pré-Frontal , Aprendizado Social , Animais , Camundongos , Tonsila do Cerebelo/fisiologia , Cálcio/metabolismo , Eletrofisiologia , Medo/fisiologia , Hipocampo/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Optogenética , Substância Cinzenta Periaquedutal/citologia , Substância Cinzenta Periaquedutal/fisiologia , Estimulação Luminosa , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Aprendizado Social/fisiologia , Reação de Congelamento Cataléptica/fisiologia
16.
Neurosci Lett ; 823: 137665, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38301912

RESUMO

Good aerobic and metabolic fitness associates with better cognitive performance and brain health. Conversely, poor metabolic health predisposes to neurodegenerative diseases. Our previous findings indicate that rats selectively bred for Low Capacity for Running (LCR) show less synaptic plasticity and more inflammation in the hippocampus and perform worse in tasks requiring flexible cognition than rats bred for High Capacity for Running (HCR). Here we aimed to determine whether hippocampal electrophysiological activity related to learning and memory would be impaired in LCR compared to HCR rats. We also studied whether an exercise intervention could even out the possible differences. We conducted in vivo recordings from the dorsal hippocampus under terminal urethane anesthesia in middle-aged sedentary males and female rats, and in females allowed to access running wheels for 6 weeks. Our results indicate stronger long-term potentiation (LTP) in the CA3-CA1 synapse in HCR than LCR rats, and in female than male rats. Compared to LCR rats, HCR rats had more dentate spikes and more gamma epochs, the occurrence of which also correlated positively with the magnitude of LTP. Voluntary running reduced the differences between female LCR and HCR rats. In conclusion, low innate fitness links to reduced hippocampal function and plasticity which can seems to improve with voluntary aerobic exercise even in middle age.


Assuntos
Potenciação de Longa Duração , Condicionamento Físico Animal , Ratos , Masculino , Feminino , Animais , Hipocampo , Eletrofisiologia , Condicionamento Físico Animal/fisiologia
18.
Elife ; 122024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345841

RESUMO

CLC-2 is a voltage-gated chloride channel that contributes to electrical excitability and ion homeostasis in many different tissues. Among the nine mammalian CLC homologs, CLC-2 is uniquely activated by hyperpolarization, rather than depolarization, of the plasma membrane. The molecular basis for the divergence in polarity of voltage gating among closely related homologs has been a long-standing mystery, in part because few CLC channel structures are available. Here, we report cryoEM structures of human CLC-2 at 2.46 - 2.76 Å, in the presence and absence of the selective inhibitor AK-42. AK-42 binds within the extracellular entryway of the Cl--permeation pathway, occupying a pocket previously proposed through computational docking studies. In the apo structure, we observed two distinct conformations involving rotation of one of the cytoplasmic C-terminal domains (CTDs). In the absence of CTD rotation, an intracellular N-terminal 15-residue hairpin peptide nestles against the TM domain to physically occlude the Cl--permeation pathway. This peptide is highly conserved among species variants of CLC-2 but is not present in other CLC homologs. Previous studies suggested that the N-terminal domain of CLC-2 influences channel properties via a "ball-and-chain" gating mechanism, but conflicting data cast doubt on such a mechanism, and thus the structure of the N-terminal domain and its interaction with the channel has been uncertain. Through electrophysiological studies of an N-terminal deletion mutant lacking the 15-residue hairpin peptide, we support a model in which the N-terminal hairpin of CLC-2 stabilizes a closed state of the channel by blocking the cytoplasmic Cl--permeation pathway.


Assuntos
Canais de Cloro CLC-2 , Animais , Humanos , Fenômenos Biofísicos , Canais de Cloro CLC-2/química , Eletrofisiologia , Mamíferos/metabolismo , Peptídeos/metabolismo , Microscopia Crioeletrônica
19.
Integr Biol (Camb) ; 162024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38291769

RESUMO

The standard model of the cell membrane potential Vm describes it as arising from diffusion currents across a membrane with a constant electric field, with zero electric field outside the cell membrane. However, the influence of Vm has been shown to extend into the extracellular space where it alters the cell's ζ-potential, the electrical potential measured a few nm from the cell surface which defines how the cell interacts with charged entities in its environment, including ions, molecules, and other cells. The paradigm arising from surface science is that the ζ-potential arises only from fixed membrane surface charge, and has consequently received little interest. However, if the ζ-potential can mechanistically and dynamically change by alteration of Vm, it allows the cell to dynamically alter cell-cell and cell-molecule interactions and may explain previously unexplained electrophysiological behaviours. Whilst the two potentials Vm and ζ are rarely reported together, they are occasionally described in different studies for the same cell type. By considering published data on these parameters across multiple cell types, as well as incidences of unexplained but seemingly functional Vm changes correlating with changes in cell behaviour, evidence is presented that this may play a functional role in the physiology of red blood cells, macrophages, platelets, sperm, ova, bacteria and cancer. Understanding how these properties will improve understanding of the role of electrical potentials and charges in the regulation of cell function and in the way in which cells interact with their environment. Insight  The zeta (ζ) potential is the electrical potential a few nm beyond the surface of any suspensoid in water. Whilst typically assumed to arise only from fixed charges on the cell surface, recent and historical evidence shows a strong link to the cell's membrane potential Vm, which the cell can alter mechanistically through the use of ion channels. Whilst these two potentials have rarely been studied simultaneously, this review collates data across multiple studies reporting Vm, ζ-potential, electrical properties of changes in cell behaviour. Collectively, this points to Vm-mediated ζ-potential playing a significant role in the physiology and activity of blood cells, immune response, developmental biology and egg fertilization, and cancer among others.


Assuntos
Neoplasias , Sêmen , Masculino , Humanos , Potenciais da Membrana , Membrana Celular/metabolismo , Eletrofisiologia , Neoplasias/metabolismo
20.
J Parkinsons Dis ; 14(1): 167-180, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38189711

RESUMO

BACKGROUND: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation. OBJECTIVE: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing. METHODS: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = 16) and controls (n = 21). Electroretinography and OCT were conducted before and after midday L-DOPA in PD participants, or repeated after ∼2 hours in controls. RESULTS: PD participants had decreased center-surround contrast suppression (p < 0.01), reduced macular visual field sensitivity (p < 0.05), color vision impairment (p < 0.01) photoreceptor dysfunction (a-wave, p < 0.01) and photoreceptor neurodegeneration (outer nuclear layer thinning, p < 0.05), relative to controls. Effect size comparison between inner and outer retinal parameters showed that photoreceptor metrics were similarly robust in differentiating the PD group from age-matched controls as inner retinal changes. Electroretinography and OCT were unaffected by L-DOPA treatment or time. CONCLUSIONS: We show that outer retinal outcomes of photoreceptoral dysfunction (decreased cone function and impaired color vision) and degeneration (i.e., outer nuclear layer thinning) were equivalent to inner retinal metrics at differentiating PD from healthy age-matched adults. These findings suggest outer retinal metrics may serve as useful biomarkers for PD.


Assuntos
Doença de Parkinson , Adulto , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Levodopa/farmacologia , Levodopa/uso terapêutico , Estudos Transversais , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Percepção Visual , Biomarcadores , Eletrofisiologia
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