Action Potential Research Articles

Synaptic-like plasticity in 2D nanofluidic memristor from competitive bicationic transport.

Synaptic plasticity, the dynamic tuning of signal transmission strength between neurons, serves as a fundamental basis for memory and learning in biological organisms. This adaptive nature of synapses is considered one of the key features contributing to the superior energy efficiency of the brain. Here, we use molecular dynamics simulations to demonstrate synaptic-like plasticity in a subnanoporous two-dimensional membrane. We show that a train of voltage spikes dynamically modifies the membrane's ionic permeability in a process involving competitive bicationic transport. This process is shown to be repeatable after a given resting period. Because of a combination of subnanometer pore size and the atomic thinness of the membrane, this system exhibits energy dissipation of 0.1 to 100 aJ per voltage spike, which is several orders of magnitude lower than 0.1 to 10 fJ per spike in the human synapse. We reveal the underlying physical mechanisms at molecular detail and investigate the local energetics underlying this apparent synaptic-like behavior.

Anti-Inflammatory and Antioxidant Activities of Eugenol: An Update

Medicinal plants are a rich source of bioactive compounds that possess pharmacological properties for preventing and treating inflammation-related diseases. Essential oils is a chemical class that contains many bioactive compounds, such as eugenol, which is capable of inhibiting or modulating the inflammatory response. This natural product emerges as a compound that promotes various biological activities, including antioxidant activity, which makes it useful in the food industry. Recently, its pharmacological applications have also been highlighted. So, this review aims to update and discuss the most recent findings on the anti-inflammatory and antioxidant activities of eugenol, along with its mechanisms of action and therapeutic potential for treating inflammation and oxidative imbalance conditions.

Comparative specialization of intrinsic cardiac neurons in humans, mice and pigs.

Intrinsic cardiac neurons (ICNs) play a crucial role in the proper functioning of the heart; yet a paucity of data pertaining to human ICNs exist. We took a multidisciplinary approach to complete a detailed cellular comparison of the structure and function of ICNs from mice, pigs and humans. Immunohistochemistry of whole and sectioned ganglia, transmission electron microscopy, intracellular microelectrode recording and dye filling for quantitative morphometry were used to define the neurophysiology, histochemistry and ultrastructure of these neurons across species. The densely packed, smaller ICNs of mouse lacked dendrites, formed axosomatic connections and had high synaptic efficacy constituting an obligatory synapse. At pig ICNs, a convergence of subthreshold cholinergic inputs onto extensive dendritic arbors supported greater summation and integration of synaptic input. Human ICNs were tonically firing, with synaptic stimulation evoking large suprathreshold EPSPs like mouse, and subthreshold potentials like pig. Ultrastructural examination of synaptic terminals revealed conserved architecture, yet small clear vesicles were larger in pigs and humans. The presence and localization of ganglionic neuropeptides was distinct, with abundant vasoactive intestinal polypeptide observed in human but not pig or mouse ganglia, and little substance P or calcitonin gene-related peptide in pig ganglia. Action potential waveforms were similar, but human ICNs had larger after-hyperpolarizations. Intrinsic excitability differed; 95% of human neurons were tonic, all pig neurons were phasic, and both phasic and tonic phenotypes were observed in mouse. In combination, this publicly accessible, multimodal atlas of ICNs from mice, pigs and humans identifies similarities and differences in the evolution of ICNs. KEY POINTS: Intrinsic cardiac neurons (ICNs) are essential to the regulation of cardiac function. We investigated the neurochemistry, morphology, ultrastructure, membrane physiology and synaptic transmission of ICNs from donated human hearts in parallel with identical studies of ICNs from mice and pigs to create a publicly accessible cellular atlas detailing the structure and function of these neurons across species. In addition to presenting foundational data on human ICNs, this comparative study identifies both conserved and derived attributes of these neurons within mammals. The findings have significant implications for understanding the regulation of cardiac autonomic function in humans and may greatly influence strategies for neuromodulation in conditions such as atrial fibrillation and heart failure.

Sodium-Selective Channelrhodopsins

Channelrhodopsins (ChRs) are light-gated ion channels originally discovered in algae and are commonly used in neuroscience for controlling the electrical activity of neurons with high precision. Initially-discovered ChRs were non-selective cation channels, allowing the flow of multiple ions, such as Na+, K+, H+, and Ca2+, leading to membrane depolarization and triggering action potentials in neurons. As the field of optogenetics has evolved, ChRs with more specific ion selectivity were discovered or engineered, offering more precise optogenetic manipulation. This review highlights the natural occurrence and engineered variants of sodium-selective channelrhodopsins (NaChRs), emphasizing their importance in optogenetic applications. These tools offer enhanced specificity in Na+ ion conduction, reducing unwanted effects from other ions, and generating strong depolarizing currents. Some of the NaChRs showed nearly no desensitization upon light illumination. These characteristics make them particularly useful for experiments requiring robust depolarization or direct Na+ ion manipulation. The review further discusses the molecular structure of these channels, recent advances in their development, and potential applications, including a proposed drug delivery system using NaChR-expressing red blood cells that could be triggered to release therapeutic agents upon light activation. This review concludes with a forward-looking perspective on expanding the use of NaChRs in both basic research and clinical settings.

Sural-to-medial femoral cutaneous amplitude ratio in early diagnosis of uremic neuropathy.

Medial femoral cutaneous (MFC) sensory nerve action potentials (SNAPs) can be easily recorded using distal stimulation. This study aimed to identify a new parameter using MFC SNAPs for the early electrophysiological diagnosis of length-dependent axonal polyneuropathy (LDAP) associated with uremic neuropathy. Patients with chronic renal failure who were referred to the electrodiagnostic laboratory due to symptoms suggesting polyneuropathy were included. Assessments encompassed neurological examination, Michigan Neuropathy Screening Instrument (MNSI), and Semmes-Weinstein monofilament test. Antidromic radial, median, ulnar, MFC, sural, and superficial peroneal sensory; median, ulnar, tibial, and peroneal motor nerve conduction studies were performed. Sural-to-radial amplitude ratio (SRAR) and sural-to-medial femoral cutaneous amplitude ratio (SMFCAR) were calculated, and their diagnostic sensitivities were compared with the age and sex matched healthy controls. Thirty-two chronic renal failure patients (mean age 60.0 ± 9.6 years) and 37 controls (60.6 ± 9 years) were included. MNSI indicated clinical polyneuropathy in 59.4% of patients, while sural SNAP amplitude was diagnostic in 78%. Median SRAR and SMFCAR values were significantly lower in patients than controls (p < .001 for both). The cut-off values for SMFCAR and SRAR were <1.82 and <0.30, respectively, both with a sensitivity of 59% and a specificity of 94%. Sural SNAP is the most sensitive parameter in the diagnosis of LDAP. SMFCAR is not superior to SRAR. If the sural SNAP amplitude is normal, SMFCAR can serve as an alternative to SRAR in dialysis patients with bilateral arteriovenous fistulae or in those unable to undergo radial NCS.

ADVANCING TOPICAL POSACONAZOLE DELIVERY: BOX BEHNKEN DESIGN MICROSPONGE HYDROGEL OPTIMIZATION AND EXTENSIVE IN VIVO INVESTIGATION

Objective: The primary aim of this study was to develop a novel hydrogel formulation containing Posaconazole (PCZ) encapsulated within microsponges. Furthermore, the study aimed to assess the permeation properties of this formulation in vivo using a mouse model. Methods: To achieve this aim, a series of seventeen trials were conducted using the Box Behnken Design methodology. These trials were designed to optimize the production of PCZ Microsponges (PCZ MS), which were subsequently incorporated into a hydrogel matrix. Skin permeation studies were then performed to evaluate the ability of the PCZ microsponge-based hydrogel to deliver the drug across the skin barrier. These studies involved comparison with a standard hydrogel formulation lacking microsponges. Results: This study assessed the efficacy of microsponge gel formulation PM-3 for drug entrapment, yield, and sustained release compared to a conventional gel. PM-3 displayed the highest entrapment efficiency of 98.5% and a yield of 95.62%, indicating a direct correlation with the 1:1 drug-polymer ratio. Moreover, PM-3 exhibited sustained drug release over 12 h, releasing 83.82% of PCZ compared to 65.31% with the normal gel, suggesting its potential for prolonged therapeutic action. These findings underscore the promise of microsponge-based hydrogels, like PM-3, in enhancing therapeutic outcomes through sustained drug release, warranting further exploration for clinical applications. Conclusion: The findings of this study highlight the promising potential of microsponge-based hydrogels as effective carriers for localized drug delivery, particularly in the context of treating skin fungal infections.

Innovative Glucagon-Based Therapies for Obesity

Abstract Obesity poses a significant global health challenge, with an alarming rise in prevalence rates. Traditional interventions, including lifestyle modifications, often fall short of achieving sustainable weight loss, ultimately leading to surgical interventions, which carry a significant burden and side effects. This necessitates the exploration of effective and relatively tolerable pharmacological alternatives. Among emerging therapeutic avenues, glucagon-based treatments have garnered attention for their potential to modulate metabolic pathways and regulate appetite. This paper discusses current research on the physiological mechanisms underlying obesity and the role of glucagon in energy homeostasis. Glucagon, traditionally recognized for its glycemic control functions, has emerged as a promising target for obesity management due to its multifaceted effects on metabolism, appetite regulation, and energy expenditure. This review focuses on the pharmacological landscape, encompassing single and dual agonist therapies targeting glucagon receptors (GcgRs), glucagon-like peptide-1 receptors (GLP-1Rs), glucose-dependent insulinotropic polypeptide receptors (GIPRs), amylin, triiodothyronine, fibroblast growth factor 21 (FGF21), and peptide tyrosine tyrosine. Moreover, novel triple-agonist therapies that simultaneously target GLP-1R, GIPR, and GcgR show promise in augmenting further metabolic benefits. This review paper tries to summarize key findings from preclinical and clinical studies, elucidating the mechanisms of action, safety profiles, and therapeutic potential of glucagon-based therapies in combating obesity and its comorbidities. Additionally, it explores ongoing research endeavors, including phase III trials, aimed at further validating the efficacy and safety of these innovative treatment modalities.

Molecular properties of a triazole–Ce(III) complex with antioxidant activity: structure, spectroscopy, and relationships with related derivatives. Influence of the ligands in the complex

A novel Ce(III) complex with the triazole ligand 2b, which presents four H-bonded sites with amino acids of the MMP-2 receptor, was synthesized. The experimental IR and Raman spectra of this Ce(III) complex were well-interpreted based on their comparison to the theoretical scaled spectra using the scaling equations determined by two procedures and four density functional theory (DFT) levels. Therefore, the structure predicted for the synthesized Ce(III) complex was clearly characterized and confirmed. The potential antioxidant action of this complex was compared with the analogous La(III) complex, and it was found that the coordination of ligand 2b with Ce(III) improves the ligand’s ability to participate in single-electron transfer (SET), as observed in the ABTS·+ assay, and this complex seems to scavenge the stable radical much more actively compared to its La(III) counterpart. Additionally, interactions with potassium superoxide and sodium hypochlorite indicate a high pro-oxidant behavior of the complex. The effects of different ligands on the geometric parameters, atomic charges, and molecular properties of the Ce(III) complex were analyzed at four DFT levels, and several relationships were clearly established. These relationships can facilitate the selection of new ligands with improved properties in the design of novel lanthanide–triazole carboxylate complexes with promising biological activity. The ligand size increase in the complexes facilitates the electronic transfer of negative charge, and the low HOMO (highest occupied molecular orbital)–LUMO (lowest unoccupied molecular orbital) energy gap indicates a large reactivity and low energy for their excitation.

An all-atom model of the human cardiac sodium channel in a lipid bilayer

Voltage-gated sodium channels (NaV) are complex macromolecular proteins that are responsible for the initial upstroke of an action potential in excitable cells. Appropriate function is necessary for many physiological processes such as heartbeat, voluntary muscle contraction, nerve conduction, and neurological function. Dysfunction can have life-threatening consequences. During the past decade, there have been significant advancements with ion channel structural characterization by CryoEM, yet descriptions of cytosolic components are often lacking. Many investigations have biophysically characterized reconstituted cytosolic components and their interactions. However, extrapolating the structural alterations and allosteric communication within an intact ion channel can be challenging. To address this, we have developed an all-atom model of the human cardiac sodium channel (NaV1.5) in a lipid bilayer with explicit salt and water. Our simulations contain descriptions of cytosolic components that are poorly predicted by AlphaFold and lacking in many CryoEM structures. Leveraging the latest advancements of the Amber force fields (ff19sb and Lipid21) and water model (OPC), our simulations improved protein backbone torsion angles and generated structural information across time (four independent one-microsecond simulations). Our analysis provided descriptions of lipid and solvent contacts and insight into the C-Terminal Domain - inactivation gate and inactivation gate - latch receptor interactions.

A sexually dimorphic signature of activity-dependent BDNF signaling on the intrinsic excitability of pyramidal neurons in the prefrontal cortex

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with strong genetic heterogeneity and more prevalent in males than females. We and others hypothesize that diminished activity-dependent neural signaling is a common molecular pathway dysregulated in ASD caused by diverse genetic mutations. Brain-derived neurotrophic factor (BDNF) is a key growth factor mediating activity-dependent neural signaling in the brain. A common single nucleotide polymorphism (SNP) in the pro-domain of the human BDNF gene that leads to a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met) significantly decreases activity-dependent BDNF release without affecting basal BDNF secretion. By using mice with genetic knock-in of this human BDNF methionine (Met) allele, our previous studies have shown differential severity of autism-like social deficits in male and female BDNF+/Met mice. Pyramidal neurons are the principal neurons in the prefrontal cortex (PFC), a key brain region for social behaviors. Here, we investigated the impact of diminished activity-dependent BDNF signaling on the intrinsic excitability of pyramidal neurons in the PFC. Surprisingly, diminished activity-dependent BDNF signaling significantly increased the intrinsic excitability of pyramidal neurons in male mice, but not in female mice. Notably, significantly decreased thresholds of action potentials were observed in male BDNF+/Met mice, but not in female BDNF+/Met mice. Voltage-clamp recordings revealed that the sodium current densities were significantly increased in the pyramidal neurons of male BDNF+/Met mice, which were mediated by increased transcriptional level of Scn2a encoding sodium channel NaV 1.2. Medium after hyperpolarization (mAHP), another important parameter to determine intrinsic neuronal excitability, is strongly associated with neuronal firing frequency. Further, the amplitudes of mAHP were significantly decreased in male BDNF+/Met mice only, which were mediated by the downregulation of Kcnn2 encoding small conductance calcium-activated potassium channel 2 (SK2). This study reveals a sexually dimorphic signature of diminished activity-dependent BDNF signaling on the intrinsic neuronal excitability of pyramidal neurons in the PFC, which provides possible cellular and molecular mechanisms underpinning the sex differences in idiopathic ASD patients and human autism victims who carry BDNF Val66Met SNP.

Clinical Features of Conduction Block in Ulnar Neuropathy at the Elbow: The Surgery of the Ulnar Nerve (SUN) Multicenter Clinical Trial.

In ulnar neuropathy at the elbow, weakness is classically a sign of severe disease. Weakness is associated with motor axonal loss as measured by decreased distal compound muscle action potential (CMAP) amplitude. Conduction block, a demyelinating phenomenon that recovers readily, can also cause weakness, creating ambiguity for the treating clinician. This cross-sectional study evaluated baseline blinded data collected from 2020-2023 from the Surgery of the Ulnar Nerve randomized controlled trial comparing in-situ decompression versus transposition procedures. Adult patients underwent electrodiagnostic testing, clinical motor and sensory testing, and completed the Michigan Hand Questionnaire and Carpal Tunnel Questionnaire. 177 patients were categorized into 3 distinct groups based on normal distal CMAP amplitudes (77 patients), presence of conduction block with or without distal CMAP amplitude loss (37 patients), or pure axonal loss with distal CMAP amplitude loss in the absence of conduction block (63 patients). Compared to the normal group, patients with conduction block had significantly decreased pinch strength and worse function domain scores on the Michigan Hand Questionnaire and Carpal Tunnel Questionnaire, but shorter duration of disease. Patients with pure axonal loss had decreased pinch strength, worse 2-point discrimination, and worse overall, function and aesthetics domain scores on the Michigan Hand Questionnaire. There was a significant interaction between the effects of conduction block and distal CMAP amplitude on pinch strength, indicating that higher degrees of conduction block resulted in more pronounced loss of pinch strength in patients with relatively preserved distal CMAP amplitude. Our findings support the paradigm that ulnar neuropathy at the elbow presenting with conduction block represents a distinct and intermediate pathophysiology, distinguished by quicker onset with less advanced neurological deficits. Prognostic Level II.

Post-procedural Brachial Neuritis: Clinical, Electrodiagnostic and Neuroimaging features.

Brachial neuritis is a monophasic condition affecting the brachial plexus and its branches, manifesting as acute shoulder and upper arm pain, followed by weakness and paresthesias. It can be triggered by antecedent events, including procedures such as surgery. Misdiagnosis and delay in diagnosis is common. Imaging is important to confirm the diagnosis of post-procedural brachial neuritis and exclude other etiologies. Clinical, electrodiagnostic, and neuroimaging features of patients with post-procedural brachial neuritis from a single quaternary care institution were identified and analyzed. Six (2 female) patients were identified with median age 62 (range 49-70) years. Antecedent procedures included 4 cervical spine surgeries, 1 rotator cuff repair, and 1 central venous catheter placement. Time to symptom onset ranged from 1-day to 2-weeks. The initial symptom for 5/6 patients was severe upper extremity pain followed by weakness. All patients had electrodiagnostic tests and MR neurography consistent with brachial neuritis. MR neurogram showed plexus and/or terminal branch abnormalities with associated muscular denervation edema. The C5 or C6 root, and/or upper trunk were always involved. The most common branches affected were the suprascapular, long thoracic, and axillary nerves. Hourglass constrictions of these nerves were seen in 3/6 patients. The average time to diagnosis was 3.4 (range 1.5-5) months. Post-procedural brachial neuritis is an underrecognized cause of acute upper extremity pain and weakness. MR neurography can exclude iatrogenic causes and document the presence of hourglass constrictions in affected nerves. Diagnostic neuroradiologists should be aware of this clinical entity and associated neuroimaging findings. HGC = hourglass constriction; EDX = electrodiagnostic; IRB = Institutional Review Board; ACDF = anterior cervical discectomy and fusion; NRS = Numerical Rating Scale; MUAP = motor unit action potential.

Role of membrane H+ transport and plasmalemma excitability in pattern formation, long-distance transport and photosynthesis of Characean algae

Illuminated giant cells of Characeae comprise alternating areas with H+ pump activity and zones with high conductivity for H+/OH–, which create counter-directed H+ flows between the medium and the cytoplasm. In areas where H+ enters the cell, the pH on the surface (pHo) increases to pH 10, while the cytoplasmic pH (pHc) decreases. The lack of the permeant substrate of photosynthesis (CO2) and the acidic pHc shift in the region of external alkaline zones redirect electron transport in chloroplasts from CO2-dependent (assimilatory) pathway to O2 reduction. This electron transport route is associated with an increase in thylakoid membrane ΔpH and an enhanced nonphotochemical quenching (NPQ) of chlorophyll excitations, which underlies strict coordination between nonuniform distributions of pHo and photosynthetic activity in resting cells. When the action potential (AP) is generated, the longitudinal pH profile is temporarily smoothed out, while the heterogeneity of the distribution of NPQ and PSII photochemical activity (YII) sharply increases. The damping of the pHo profile is due to the suppression of the H+ pump and passive H+ conductance under the influence of an almost 100-fold increase in the cytoplasmic of Ca2+ level ([Ca2+]c) during AP. The increase in [Ca2+]c stimulates photoreduction of O2 in chloroplasts under external alkaline zones and, at the same time, arrests the cytoplasmic streaming, which causes the accumulation of excess amounts of H2O2 in the cytoplasm in areas of intense production of this metabolite, with a weak effect on areas of CO2 assimilation. These changes enhance the nonuniform distribution of cell photosynthesis and account for the long-term oscillations of chlorophyll fluorescence Fm' and the quantum efficiency of linear electron flow in microscopic cell areas after the AP generation.

Involvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder

BackgroundAbnormal sensory perception, particularly pain insensitivity (PAI), is a typical symptom of autism spectrum disorder (ASD). Despite the role of myelin metabolism in the regulation of pain perception, the mechanisms underlying ASD-related PAI remain unclear.MethodsThe pain-associated gene sphingosine-1-phosphate receptor 1 (S1PR1) was identified in ASD samples through bioinformatics analysis. Its expression in the dorsal root ganglion (DRG) tissues of BTBR ASD model mice was validated using RNA-seq, western blot, RT-qPCR, and immunofluorescence. Pain thresholds were assessed using the von Frey and Hargreaves tests. Patch-clamp techniques measured KCNQ/M channel activity and neuronal action potentials. The expression of S1PR1, KCNQ/M, mitogen-activated protein kinase (MAPK), and cyclic AMP/protein kinase A (cAMP/PKA) signaling proteins was analyzed before and after inhibiting the S1P-S1PR1-KCNQ/M pathway via western blot and RT-qPCR.ResultsThrough integrated transcriptomic analysis of ASD samples, we identified the upregulated gene S1PR1, which is associated with sphingolipid metabolism and linked to pain perception, and confirmed its role in the BTBR mouse model of ASD. This mechanism involves the regulation of KCNQ/M channels in DRG neurons. The enhanced activity of KCNQ/M channels and the decreased action potentials in small and medium DRG neurons were correlated with PAI in a BTBR mouse model of ASD. Inhibition of the S1P/S1PR1 pathway rescued baseline insensitivity to pain by suppressing KCNQ/M channels in DRG neurons, mediated through the MAPK and cAMP/PKA pathways. Investigating the modulation and underlying mechanisms of the non-opioid pathway involving S1PR1 will provide new insights into clinical targeted interventions for PAI in ASD.ConclusionsS1PR1 may contribute to PAI in the PNS in ASD. The mechanism involves KCNQ/M channels and the MAPK and cAMP/PKA signaling pathways. Targeting S1PR1 in the PNS could offer novel therapeutic strategies for the intervention of pain dysesthesias in individuals with ASD.

Unveiling the cell biology of hippocampal neurons with dendritic axon origin.

In mammalian axon-carrying-dendrite (AcD) neurons, the axon emanates from a basal dendrite, instead of the soma, to create a privileged route for action potential generation at the axon initial segment (AIS). However, it is unclear how such unusual morphology is established and whether the structure and function of the AIS in AcD neurons are preserved. By using dissociated hippocampal cultures as a model, we show that the development of AcD morphology can occur prior to synaptogenesis and independently of the in vivo environment. A single precursor neurite first gives rise to the axon and then to the AcD. The AIS possesses a similar cytoskeletal architecture as the soma-derived AIS and similarly functions as a trafficking barrier to retain axon-specific molecular composition. However, it does not undergo homeostatic plasticity, contains lesser cisternal organelles, and receives fewer inhibitory inputs. Our findings reveal insights into AcD neuron biology and underscore AIS structural differences based on axon onset.

Action potential threshold variability for different electrostimulation models and its potential impact on occupational exposure limit values.

Occupational exposure limit values (ELVs) for body internal electric fields can be derived from thresholds for action potential generation. These thresholds can be calculated with electrostimulation models. The spatially extended nonlinear node model (SENN) is often used to determine such thresholds. Important parameters of these models are the membrane channel dynamics describing the ionic transmembrane currents as well as the temperature at which the models operate. This work compares action potential thresholds for five different membrane channel dynamics used with the SENN model. Furthermore, two more detailed double-cable models by Gaines et al. (MRG-Sensory and MRG-Motor) are also considered in this work. Thresholds calculated with the SENN model and the MRG models are compared for frequencies between 1 Hz and 100 kHz and temperatures at 22°C and 37°C. Results show that MRG thresholds are lower than SENN thresholds. Deriving alternative ELVs from these thresholds shows that the alternative ELVs can change significantly with different ion channel dynamics (up to a factor of 22). Using the double cable model could lead to approximately ten times lower alternative exposure limit values. On the contrary, using the SENN model with different membrane channel dynamics could also lead to higher alternative exposure limit values. Therefore, future exposure guidelines should take the influence of different electrostimulation models into account when deriving ELVs.

Distinct Ventral Hippocampus Network Properties inDissociated Cultures.

Extensive research has been focused in the past century on structural, physiological, and molecular attributes of the hippocampus. This interest was created by the unique involvement of the hippocampus in cognitive and affective functions of the brain. Functional analysis revealed that the hippocampus has divergent properties along its axial dimension to the extent that the dorsal sector (dorsal hippocampus, DH) has different connections with the rest of the brain than those of the ventral sector (VH). Still, longitudinal pathways connect the DH with the VH and dampen the functional differences between the sectors. To be able to identify the intrinsic functional difference between the DH and VH, we produced dissociated monolayer cultures from prenatal DH and VH and examined their properties at 10-20 days after plating by imaging the spontaneous activity of the network using Fluo-2 AM, a calcium indicator. Surprisingly, while DH and VH sectors produced dissociated cultures with similar morphological attributes, VH cultures were more active spontaneously than DH cultures. Furthermore, when stimulated to produce action potentials, VH neurons triggered network bursts in postsynaptic neurons more often than DH cultures. Finally, in both DH and VH cultures, electrical stimulation of single cells produced network bursts in response to a burst of action potentials rather than to single spikes. These experiments indicate that even in dissociated cultures, neurons of the VH are more excitable and sensitive to electrical stimulation than DH; hence, they are more likely to generate network bursts and epileptic seizures, as suggested for invivo brains.

Biocontrol Potential and Mechanisms of Action of Plant Associated Yeast

Biocontrol Potential and Mechanisms of Action of Plant Associated Yeast

Effect of Calcium on the Characteristics of Action Potential Under Different Electrical Stimuli

This study investigates the role of calcium ions in the release of action potentials by comparing two models based on the framework: the standard HH model and a HH + Ca model that incorporates calcium ion channels. Purkinje cells’ responses to four types of electrical current stimuli—constant direct current, step current, square wave current, and sine current—were simulated to analyze the impact of calcium on action potential characteristics. The results indicate that, under the constant direct current stimulation, the action potential firing frequency of both models increased with the escalating current intensity, while the delay time of the first action potential decreased. However, when the current intensity exceeded a specific threshold, the peak amplitude of the action potential gradually diminished. The HH + Ca model exhibited a longer delay in the first action potential compared to the HH model but maintained an action potential release under stronger currents. In response to the step current, both models showed an increased action potential frequency with a higher current, but the HH + Ca model generated subthreshold oscillations under weak currents. With the square wave current, the action potential frequency increased, though the HH + Ca model experienced suppression under high-frequency weak currents. Under the sine current, the action potential frequency rose, with the HH + Ca model showing less depression near the sine peak due to calcium’s role in modulating membrane potential. These findings suggest that calcium ions contribute to a more stable action potential release under varying stimuli.

In silico analysis of ventricular action potential with a current-voltage-time representation: Thresholds, membrane resistance, repolarization reserve.

The waveform of ventricular action potential (AP) is a key determinant of the cardiac cycle, a marker of beating pathophysiology, and a target for anti-arrhythmic drug design. The information contained in the waveform, though, is limited to the actual dynamics of the AP under consideration. By measuring quasi-instantaneous current-voltage relationships during repolarization, I propose a three-dimensional representation of the ventricular AP which includes potential dynamic responses that the beat can show when electrically perturbed. This representation is described in the case of a numerically reconstructed ventricular AP, but it can be, at least partially, derived in real cardiomyocytes. Simulation allows to disclose the potentialities and the limitations of the approach, that can be extended to any non-cardiac AP. By reporting, at any AP time, the ion current available within the physiological membrane potential range at that time, the representation makes all together available: (1) refractory period, (2) thresholds for eliciting full or calcium-driven APs, (3) threshold for all-or-none repolarization, (4) membrane resistance during repolarization, (5) the safety of membrane repolarization. It provides further evidence of a negative membrane resistance during the late phase of ventricular AP and a quantitative estimate of repolarization reserve (RR), key determinants of repolarization dynamics.