Action Potential Conduction Velocity Research Articles

Adherens junction engagement regulates functional patterning of the cardiac pacemaker cell lineage.

Cardiac pacemaker cells (CPCs) rhythmically initiate the electrical impulses that drive heart contraction. CPCs display the highest rate of spontaneous depolarization in the heart despite being subjected to inhibitory electrochemical conditions that should theoretically suppress their activity. While several models have been proposed to explain this apparent paradox, the actual molecular mechanisms that allow CPCs to overcome electrogenic barriers to their function remain poorly understood. Here, we have traced CPC development at single-cell resolution and uncovered a series of cytoarchitectural patterning events that are critical for proper pacemaking. Specifically, our data reveal that CPCs dynamically modulate adherens junction (AJ) engagement to control characteristics including surface area, volume, and gap junctional coupling. This allows CPCs to adopt a structural configuration that supports their overall excitability. Thus, our data have identified a direct role for local cellular mechanics in patterning critical morphological features that are necessary for CPC electrical activity.

Fully Implantable Plantar Cutaneous Augmentation System for Rats Using Closed-loop Electrical Nerve Stimulation.

Plantar cutaneous feedback plays an important role in stable and efficient gait, by modulating the activity of ankle dorsi- and plantar-flexor muscles. However, central and peripheral nervous system trauma often decrease plantar cutaneous feedback and/or interneuronal excitability in processing the plantar cutaneous feedback. In this study, we tested a fully implantable neural recording and stimulation system augmenting plantar cutaneous feedback. Electromyograms were recorded from the medial gastrocnemius muscle for stance phase detection, while biphasic stimulation pulses were applied to the distal-tibial nerve during the stance phase to augment plantar cutaneous feedback. A Bluetooth low energy and a Qi-standard inductive link were adopted for wireless communication and wireless charging, respectively. To test the operation of the system, one intact rat walked on a treadmill with the electrical system implanted into its back. Leg kinematics were recorded to identify the stance phase. Stimulation was applied, with a 250-ms onset delay from stance onset and 200-ms duration, resulting in the onset at 47.58±2.82% of stance phase and the offset at 83.49±4.26% of stance phase (Mean±SEM). The conduction velocity of the compound action potential (31.2 m/s and 41.6 m/s at 1·T and 2·T, respectively) suggests that the evoked action potential was characteristic of an afferent volley for cutaneous feedback. We also demonstrated successful wireless charging and system reset functions. The experimental results suggest that the presented implantable system can be a valuable neural interface tool to investigate the effect of plantar cutaneous augmentation on gait in a rat model.

Inducibility, but not stability, of atrial fibrillation is increased by NOX2 overexpression in mice.

AimsGp91-containing NADPH oxidases (NOX2) are a significant source of myocardial superoxide production. An increase in NOX2 activity accompanies atrial fibrillation (AF) induction and electrical remodelling in animal models and predicts incident AF in humans; however, a direct causal role for NOX2 in AF has not been demonstrated. Accordingly, we investigated whether myocardial NOX2 overexpression in mice (NOX2-Tg) is sufficient to generate a favourable substrate for AF and further assessed the effects of atorvastatin, an inhibitor of NOX2, on atrial superoxide production and AF susceptibility.Methods and resultsNOX2-Tg mice showed a 2- to 2.5-fold higher atrial protein content of NOX2 compared with wild-type (WT) controls, which was associated with a significant (twofold) increase in NADPH-stimulated superoxide production (2-hydroxyethidium by HPLC) in left and right atrial tissue homogenates (P = 0.004 and P = 0.019, respectively). AF susceptibility assessed in vivo by transoesophageal atrial burst stimulation was modestly increased in NOX2-Tg compared with WT (probability of AF induction: 88% vs. 69%, respectively; P = 0.037), in the absence of significant alterations in AF duration, surface ECG parameters, and LV mass or function. Mechanistic studies did not support a role for NOX2 in promoting electrical or structural remodelling, as high-resolution optical mapping of atrial tissues showed no differences in action potential duration and conduction velocity between genotypes. In addition, we did not observe any genotype difference in markers of fibrosis and inflammation, including atrial collagen content and Col1a1, Il-1β, Il-6, and Mcp-1 mRNA. Similarly, NOX2 overexpression did not have consistent effects on RyR2 Ca2+ leak nor did it affect PKA or CaMKII-mediated RyR2 phosphorylation. Finally, treatment with atorvastatin significantly inhibited atrial superoxide production in NOX2-Tg but had no effect on AF induction in either genotype.ConclusionTogether, these data indicate that while atrial NOX2 overexpression may contribute to atrial arrhythmogenesis, NOX2-derived superoxide production does not affect the electrical and structural properties of the atrial myocardium.

Periaxonal and nodal plasticities modulate action potential conduction in the adult mouse brain

Central nervous system myelination increases action potential conduction velocity. However, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials and facilitate information processing within cortical and associative circuits. Here, we show that myelin sheaths, supported by mature oligodendrocytes, remain plastic in the adult mouse brain and undergo subtle structural modifications to influence action potential conduction velocity. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and robustly alters action potential conduction velocity. Because aptitude in the spatial learning task was found to correlate with action potential conduction velocity in the fimbria-fornix pathway, modifying the axon-glial configuration may be a mechanism that facilitates learning in the adult mouse brain.

Electrophysiological properties of maxillary trigeminal Aβ-afferent neurons of rats.

Aβ-afferents in maxillary or V2 trigeminal ganglion (TG) neurons are somatosensory neurons that may be involved in both non-nociceptive and nociceptive functions in orofacial regions. However, electrophysiological properties of these V2 trigeminal Aβ-afferent neurons have not been well characterized so far. Here, we used rat ex vivo trigeminal nerve preparations and applied patch-clamp recordings to large-sized V2 TG neurons to characterize their electrophysiological properties. All the cells recorded had afferent conduction velocities in the range of Aβ-afferent conduction speeds. However, these V2 trigeminal Aβ-afferent neurons displayed different action potential (AP) properties. APs showed fast kinetics in some cells but slow kinetics with shoulders in repolarization phases in other cells. Based on the derivatives of voltages in AP repolarization with time (dV/dt), we classified V2 trigeminal Aβ-afferent neurons into four types: type I, type II, type IIIa and type IIIb. Type I V2 trigeminal Aβ-afferent neurons had the largest dV/dt of repolarization, the fastest AP conduction velocities, the shortest AP and afterhyperpolarization (AHP) durations, and the highest AP success rates. In contrast, type IIIb V2 trigeminal Aβ-afferent neurons had the smallest dV/dt of AP repolarization, the slowest AP conduction velocities, the longest AP and AHP durations, and the lowest AP success rates. The type IIIb cells also had significantly lower voltage-activated K+ currents. For type II and type IIIa V2 trigeminal Aβ-afferent neurons, AP parameters were in the range between those of type I and type IIIb V2 trigeminal Aβ-afferent neurons. Our electrophysiological classification of V2 trigeminal Aβ-afferent neurons may be useful in future to study their non-nociceptive and nociceptive functions in orofacial regions.

Prevalence of Accessory Deep Peroneal Nerve in Sample of Bosnia and Herzegovina Subjects: an Electrophysiological Study.

Background:The accessory deep peroneal nerve (ADPN) is as an anomalous nerve derived from the superficial peroneal nerve or its branch and supplies motor innervations for extensor digitorum brevis (EDB) and sensory innervations for the lateral part of the ankle and foot regions. It is the most common anomalous innervation present in the lower limb.Objective:The aim of this study was to determine the prevalence of ADPN electrophysiologically in a sample of Bosnia and Herzegovina subjects who referred to an electromyography lab.Methods:This cross-sectional descriptive study included 316 lower limbs from 171 subjects referred for electrodiagnostic studies to Electromyography Lab, Department of Neurology, University Clinical Center Tuzla (Bosnia and Herzegovina) (102 females/60% and 69/40%) males). Motor nerve conduction studies for the peroneal nerve and ADPN were done. Compound muscle action potential (CMAP) and nerve conduction velocity (NCV) of deep peroneal nerve (DPN) were measured by using EMG machine by stimulating DPN at knee, ankle and lateral malleolus areas accordingly, with recording from extensor digitorum brevis (EDB) muscle.Results:ADPN was found in 46 (14.5%) of 316 legs. ADPN was found in 18 (39.1%) right lower limbs and 28 (60.9%) left lower limbs. Ten subjects (5.8%) had bilateral ADPN. There was no statistically significant difference between the occurrence of ADPN in women versus men (p=0.757), as well as in right versus left legs (p=0.237).Conclusion:This study demonstrated that ADPN prevalence, in a sample of Bosnia and Herzegovina subjects who referred to an electromyography lab is 14.5%. Recognition of ADPN is very important for proper interpretation of lower limbs electrophysiological data.

Modeling action potential reversals in tunicate hearts.

Tunicates are small invertebrates which possess a unique ability to reverse flow in their hearts. Scientists have debated various theories regarding how and why flow reversals occur. Here we explore the electrophysiological basis for reversals by simulating action potential propagation in an idealized model of the tubelike tunicate heart. Using asymptotic formulas for action potential duration and conduction velocity, we propose tunicate-specific parameters for a two-current ionic model of the action potential. Then, using a kinematic model, we derive analytical criteria for reversals to occur. These criteria inform subsequent numerical simulations of action potential propagation in a fiber paced at both ends. In particular, we explore the role that variability of pacemaker firing rates plays in generating reversals, and we identify various favorable conditions for triggering retrograde propagation. Our analytical framework extends to other species; for instance, it can be used to model competition between the sinoatrial node and abnormal ectopic foci in human heart tissue.

A survey of pathways for mechano-electric coupling in the atria

Mechano-electric coupling (MEC) in atrial tissue has received sparse investigation to date, despite the well-known association between chronic atrial dilation and atrial fibrillation (AF). Of note, no fewer than six different mechanisms pertaining to stretch-activated channels, cellular capacitance and geometric effects have been identified in the literature as potential players. In this mini review, we briefly survey each of these pathways to MEC. We then perform computational simulations using single cell and tissue models in presence of various stretch regimes and MEC pathways. This allows us to assess the relative significance of each pathway in determining action potential duration, conduction velocity and rotor stability. For chronic atrial stretch, we find that stretch-induced alterations in membrane capacitance decrease conduction velocity and increase action potential duration, in agreement with experimental findings. In the presence of time-dependent passive atrial stretch, stretch-activated channels play the largest role, leading to after-depolarizations and rotor hypermeandering. These findings suggest that physiological atrial stretches, such as passive stretch during the atrial reservoir phase, may play an important part in the mechanisms of atrial arrhythmogenesis.

Effects of different nerve autografts on greater auricular nerve deficit in rabbits

Effects of different nerve autografts on greater auricular nerve deficit in rabbits

Protein expression profiles in murine ventricles modeling catecholaminergic polymorphic ventricular tachycardia: effects of genotype and sex.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with mutations in the cardiac ryanodine receptor (RyR2). These result in stress-induced ventricular arrhythmic episodes, with clinical symptoms and prognosis reported more severe in male than female patients. Murine homozygotic RyR2-P2328S (RyR2S/S ) hearts replicate the proarrhythmic CPVT phenotype of abnormal sarcoplasmic reticular Ca2+ leak and disrupted Ca2+ homeostasis. In addition, RyR2S/S hearts show decreased myocardial action potential conduction velocities (CV), all features implicated in arrhythmic trigger and substrate. The present studies explored for independent and interacting effects of RyR2S/S genotype and sex on expression levels of molecular determinants of Ca2+ homeostasis (CASQ2, FKBP12, SERCA2a, NCX1, and CaV 1.2) and CV (NaV 1.5, Connexin (Cx)-43, phosphorylated-Cx43, and TGF-β1) in mice. Expression levels of Ca2+ homeostasis proteins were not altered, hence implicating abnormal RyR2 function alone in disrupted cytosolic Ca2+ homeostasis. Furthermore, altered NaV 1.5, phosphorylated Cx43, and TGF-β1 expression were not implicated in the development of slowed CV. By contrast, decreased Cx43 expression correlated with slowed CV, in female, but not male, RyR2S/S mice. The CV changes may reflect acute actions of the increased cytosolic Ca2+ on NaV 1.5 and Cx43 function.

Comparison of Corticosteroid Injection Dosages in Mild to Moderate Idiopathic Carpal Tunnel Syndrome: A Randomized Controlled Trial

ObjectivesTo evaluate whether the therapeutic effect of ultrasound-guided injections with 10 mg or 40 mg triamcinolone acetonide (TA) was dose-dependent in patients with idiopathic mild to moderate carpal tunnel syndrome (CTS). DesignProspective, double-blind, randomized controlled study with 12 weeks of follow-up. SettingRehabilitation outpatient clinic of a single medical center. ParticipantsPatients with CTS (N=56). InterventionParticipants were randomly assigned to 2 treatment groups for injection: (A) 40 mg TA+2% lidocaine hydrochloride or (B) 10 mg TA+2% lidocaine hydrochloride. Main Outcome MeasuresParticipants were evaluated using visual analog scale (VAS) and Boston Carpal Tunnel Questionnaire (BCTQ, including Symptom Severity Scale [SSS] and Functional Status Scale [FSS]) at baseline and 6 and 12 weeks after injection). Nerve conduction studies, including parameters of distal motor latency, amplitude of compound motor action potential, amplitude of sensory nerve action potential and sensory nerve conduction velocity of median nerve, and the patient’s subjective impression of improvement, were recorded before injection and 6 and 12 weeks after injection. ResultsNo significant differences were observed in baseline demographic characteristics and clinical evaluations. The parameters in group A and B at baseline, 6 weeks, and 12 weeks were (1) SSS: 2.17±0.14, 1.19±0.04, and 1.34±0.09 and 1.87±0.11, 1.21±0.07, and 1.26±0.04; (2) FSS: 1.63±0.07, 1.27±0.06, and 1.33±0.08 and 1.50±0.10, 1.18±0.05, and 1.26±0.05; (3) VAS: 6.4±0.3, 2.2±0.3, and 3.0±0.1 and 6.7±0.3, 2.0±0.3, and 3.1±0.3, respectively, and significantly decreased after 6 and 12 weeks in both treatment groups (P<.05). All parameters of nerve conduction studies improved in both groups after 12 weeks (P<.05). VAS, BCTQ, and nerve conduction studies did not show significant intergroup differences after 6 and 12 weeks. ConclusionIn patients with idiopathic mild to moderate CTS, ultrasound-guided injection with 10 and 40 mg TA yield similar improvements in BCTQ, VAS, and nerve conduction studies at the 12-week follow-up.

C1orf194 deficiency leads to incomplete early embryonic lethality and dominant intermediate Charcot-Marie-Tooth disease in a knockout mouse model.

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy and shows clinical and genetic heterogeneity. Mutations in C1orf194 encoding a Ca2+ regulator in neurons and Schwann cells have been reported previously by us to cause CMT disease. In here, we further investigated the function and pathogenic mechanism of C1or194 by generating C1orf194 knockout (KO) mice. Homozygous mutants of C1orf194 mice exhibited incomplete embryonic lethality, characterized by differentiation abnormalities and stillbirth on embryonic days 7.5-15.5. Heterozygous and surviving homozygous C1orf194 KO mice developed motor and sensory defects at the age of 4months. Electrophysiologic recordings showed decreased compound muscle action potential and motor nerve conduction velocity in the sciatic nerve of C1orf194-deficient mice as a pathologic feature of dominant intermediate-type CMT. Transmission electron microscopy analysis revealed demyelination and axonal atrophy in the sciatic nerve as well as swelling and loss of mitochondrial matrix and other abnormalities in axons and Schwann cells. A histopathologic examination showed a loss of motor neurons in the anterior horn of the spinal cord and muscle atrophy. Shorter internodal length between nodes of Ranvier and Schmidt-Lanterman incisures was detected in the sciatic nerve of affected animals. These results indicate that C1orf194 KO mice can serve as an animal model of CMT with a severe dominant intermediate CMT phenotype that can be used to investigate the molecular mechanisms of the disease and evaluate the efficacy of therapeutic strategies.

Cardiometabolic risk factors as determinants of peripheral nerve function: the Maastricht Study

Aims/hypothesisWe aimed to examine associations of cardiometabolic risk factors, and (pre)diabetes, with (sensorimotor) peripheral nerve function.MethodsIn 2401 adults (aged 40–75 years) we previously determined fasting glucose, HbA1c, triacylglycerol, HDL- and LDL-cholesterol, inflammation, waist circumference, blood pressure, smoking, glucose metabolism status (by OGTT) and medication use. Using nerve conduction tests, we measured compound muscle action potential, sensory nerve action potential amplitudes and nerve conduction velocities (NCVs) of the peroneal, tibial and sural nerves. In addition, we measured vibration perception threshold (VPT) of the hallux and assessed neuropathic pain using the DN4 interview. We assessed cross-sectional associations of risk factors with nerve function (using linear regression) and neuropathic pain (using logistic regression). Associations were adjusted for potential confounders and for each other risk factor. Associations from linear regression were presented as standardised regression coefficients (β) and 95% CIs in order to compare the magnitudes of observed associations between all risk factors and outcomes.ResultsHyperglycaemia (fasting glucose or HbA1c) was associated with worse sensorimotor nerve function for all six outcome measures, with associations of strongest magnitude for motor peroneal and tibial NCV, βfasting glucose = −0.17 SD (−0.21, −0.13) and βfasting glucose = −0.18 SD (−0.23, −0.14), respectively. Hyperglycaemia was also associated with higher VPT and neuropathic pain. Larger waist circumference was associated with worse sural nerve function and higher VPT. Triacylglycerol, HDL- and LDL-cholesterol, and blood pressure were not associated with worse nerve function; however, antihypertensive medication usage (suggestive of history of exposure to hypertension) was associated with worse peroneal compound muscle action potential amplitude and NCV. Smoking was associated with worse nerve function, higher VPT and higher risk for neuropathic pain. Inflammation was associated with worse nerve function and higher VPT, but only in those with type 2 diabetes. Type 2 diabetes and, to a lesser extent, prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were associated with worse nerve function, higher VPT and neuropathic pain (p for trend <0.01 for all outcomes).Conclusions/interpretationHyperglycaemia (including the non-diabetic range) was most consistently associated with early-stage nerve damage. Nonetheless, larger waist circumference, inflammation, history of hypertension and smoking may also independently contribute to worse nerve function.

Conduction Velocity of Muscle Action Potential of Knee Extensor Muscle During Evoked and Voluntary Contractions After Exhaustive Leg Pedaling Exercise.

PurposeMuscle fiber conduction velocity (CV) has been developed to estimate neuromuscular fatigue and measured during voluntary (VC) and electrically evoked (EC) contractions. Since CV during VC and EC reflect different physiological phenomena, the two parameters would show inconsistent changes under the conditions of neuromuscular fatigue. We investigated the time-course changes of CV during EC and VC after fatiguing exercise.MethodsIn 14 young males, maximal voluntary contraction (MVC) of knee extensor muscles, CV during electrical stimulation (CV-EC) and MVC (CV-VC) were measured before and immediately, 30 min, 60 min, 120 min, and 24 h after exhaustive leg pedaling exercise.ResultsCV-EC significantly increased immediately after the fatiguing exercise (p < 0.05) and had a significant negative correlation with MVC in merged data from all time-periods (r = −0.511, p < 0.001). CV-VC significantly decreased 30, 60, and 120 min after the fatiguing exercise (p < 0.05) and did not show any correlations with MVC (p > 0.05).ConclusionThese results suggest that CV during EC and VC exhibits different time-course changes, and that CV during EC may be appropriate to estimate the degree of neuromuscular fatigue after fatiguing pedaling exercise.

Optical mapping of the pig heart in situ under artificial blood circulation

The emergence of optical imaging has revolutionized the investigation of cardiac electrical activity and associated disorders in various cardiac pathologies. The electrical signals of the heart and the propagation pathways are crucial for elucidating the mechanisms of various cardiac pathological conditions, including arrhythmia. The synthesis of near-infrared voltage-sensitive dyes and the voltage sensitivity of the FDA-approved dye Cardiogreen have increased the importance of optical mapping (OM) as a prospective tool in clinical practice. We aimed to develop a method for the high-spatiotemporal-resolution OM of the large animal hearts in situ using di-4-ANBDQBS and Cardiogreen under patho/physiological conditions. OM was adapted to monitor cardiac electrical behaviour in an open-chest pig heart model with physiological or artificial blood circulation. We detail the methods and display the OM data obtained using di-4-ANBDQBS and Cardiogreen. Activation time, action potential duration, repolarization time and conduction velocity maps were constructed. The technique was applied to track cardiac electrical activity during regional ischaemia and arrhythmia. Our study is the first to apply high-spatiotemporal-resolution OM in the pig heart in situ to record cardiac electrical activity qualitatively under artificial blood perfusion. The use of an FDA-approved voltage-sensitive dye and artificial blood perfusion in a swine model, which is generally accepted as a valuable pre-clinical model, demonstrates the promise of OM for clinical application.

Electrodiagnostic reference data for sensory nerve conduction studies in Saudi Arabia.

Objectives:To estimate reference data for the commonly performed sensory nerve conduction studies (NCS) using a cohort of healthy subjects from Saudi ArabiaMethods:This is a cross-sectional study conducted between May 2015, and June 2019. Sensory nerve action potential (SNAP) amplitude, conduction velocity (CV), and peak latency (PL) were recorded. Associations between these parameters and the covariates (age, sex, height, weight, and body mass index) were tested with Pearson correlations. Reference data were then derived using the lowest percentile that could be reliably determined for SNAP amplitude and CV. Reference data were derived using the highest percentile for PL.Results:Upper and lower limb sensory NCS were performed in 127 and 137 participants, respectively. Age was the only covariate that required adjustment for estimation of SNAP amplitude. Therefore, a prediction model was generated for each nerve. Percentile estimation for PL and CV did not require adjustment for any of the covariates. Hence, it was derived for all the subjects pooled together.Conclusion:The sensory NCS reference data were comparable to the data from other countries. However, minimal differences were observed. Further studies are required with a focus on the older age group. Received 2nd August 2019. Accepted 11th December 2019.

Adrenoceptor Responses in Human Embryonic Stem Cell-Derived Cardiomyocytes: a Special Focus on Electrophysiological Property.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have become a promising cell source for cardiovascular research. The electrophysiological characteristic of hESC-CMs has been generally studied, but little is known about electrophysiological response to adrenergic receptor (AR) activation. This study aims to characterize electrophysiological response of hESC-CMs to adrenergic stimulation in terms of the conduction velocity (CV) and action potential (AP) shape. The H9 hESC-CMs were acquired by a classic differentiation protocol and cultured to achieve confluent cell monolayers. The AP shape and CV among the monolayers were recorded using optical mapping during electrophysiological and pharmacological stimulation experiments. Quantitative real-time polymerase chain reaction and Western blot were adopted to determine the expression levels of Connexin and ion channel gene and protein. Chronic β-AR stimulation by isoproterenol for 24 hours in hESC-CM monolayers increased CV by approximately 50%, whereas α-AR or acute β-AR stimulation had no significant effect; chronic β-AR stimulation resulted in a significant Connexin (Cx) 43 and Nav1.5 upregulation at both protein and mRNA level. Isoproterenol-induced CV accelerating and Cx43 and Nav1.5 upregulation in hESC-CMs, which was attenuated by selective β1-adrenoceptor antagonist CGP 20712A but not selective β2-antagonist ICI 118551. Moreover, pretreatment with protein kinase A (PKA) inhibitor H89, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (MEK) inhibitor SB203580, and MAPK inhibitor PD98059 suppressed the isoproterenol-induced CV accelerating and Cx43 upregulation, whereas it had no significant effect on Nav1.5 upregulation. The AP shape in hESC-CM monolayers was less susceptible by either β-AR or α-AR stimulation. It was β1-AR not β2-AR contributing to the modification of conduction velocity among hESC-CM monolayers. Chronic β1-AR stimulation accelerates CV by upregulating Cx43 via PKA/MEK/MAPK pathway. SIGNIFICANCE STATEMENT: These data provide new insight into the electrophysiological characteristics of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and depict a concise signaling pathway in the adrenergic receptor (AR) regulation of action potential shape and electrical propagation across hESC-CM monolayer. It is β1-AR not β2-AR contributing to the modification of conduction velocity in hESC-CMs and accelerating conduction velocity by upregulating Connexin 43 via protein kinase A/ mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase/MAPK pathway.

The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction.

Neurons have a membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin. Here, combining chemical and genetic gain- and loss-of-function assays, we show that in rat hippocampal neurons the MPS is an actomyosin network that controls axonal expansion and contraction. Using super-resolution microscopy, we analyzed the localization of axonal non-muscle myosin II (NMII). We show that active NMII light chains are colocalized with actin rings and organized in a circular periodic manner throughout the axon shaft. In contrast, NMII heavy chains are mostly positioned along the longitudinal axonal axis, being able to crosslink adjacent rings. NMII filaments can play contractile or scaffolding roles determined by their position relative to actin rings and activation state. We also show that MPS destabilization through NMII inactivation affects axonal electrophysiology, increasing action potential conduction velocity. In summary, our findings open new perspectives on axon diameter regulation, with important implications in neuronal biology.

Dose-dependent effect of the pulsed Nd:YAG laser in the treatment of crushed sciatic nerve in Wister rats: an experimental model

The objective of the study was to investigate the efficacy of three energy densities 4, 10, and 50J/cm2 of pulsed Nd:YAG laser for the treatment of crushed sciatic nerve in Wister rats by evaluating changes in the sciatic functional index and the electrophysiology.A total of 180 Wistar rats were involved in the study. Rats were randomly assigned to five groups. Rats were subjected to the sciatic nerve crushing. Control negative (CONT-ve), which received no crushing; control positive (CONT+ve), which received crushing with no laser; and HILT-4, HILT-10, and HILT-50 groups, which received pulsed Nd:YAG laser (10Hz, 360mJ/cm2) with energy densities 4, 10, and 50J/cm2, respectively. The SFI, the amilitude of compound motor action potential (CMAP) and sciatic motor nerve conduction velocity (MNCV) were measured before and after seven, 14, and 21days after crushing. For the SFI and electrophysiological analysis, repeated measures ANOVA is used, followed by Bonferroni's repeated-measures test. Statistical significance was set at p < 0.05. After oneweek, there was no significant difference in SFI, CMAP, and MNCV among the three laser groups with significant changes between them and CONT-ve and CONT+ve groups. There was a significant increase in either CMAP amplitude or MNCV after 14days with significant decrease in the SFI after 21days among all treatment groups. The pulsed Nd:YAG laser applied with energy densities 4, 10, and 50J/cm2 significantly decreased the SFI and increased the CMAP and MNCV of the crushed sciatic nerve in Wister rats. Among laser doses, the difference in the rate of recovery in the electrophysiology was found after twoweeks while in the SFI after threeweeks. The improvement after the nerve injury was time and dose dependent.

Arrhythmia susceptibility in a rat model of acute atrial dilation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, associated with an increased risk of stroke and heart failure. Acute AF occurs in response to sudden increases of atrial hemodynamic load, leading to atrial stretch. The mechanisms of stretch-induced AF were investigated in large mammals with controversial results. We optimized an approach to monitor rat atrial electrical activity using a red-shifted voltage sensitive dye (VSD). The methodology includes cauterization of the main ventricular coronary arteries, allowing improved atrial staining by the VSD and appropriate atrial perfusion for long experiments. Next, we developed a rat model of acute biatrial dilation (ABD) through the insertion of latex balloons into both atria, which could be inflated with controlled volumes. A chronic model of atrial dilation (spontaneous hypertensive rats; SHR) was used for comparison. ABD was performed on atria from healthy Wistar-Kyoto (WKY) rats (WKY-ABD). The atria were characterized in terms of arrhythmias susceptibility, action potential duration and conduction velocity. The occurrence of arrhythmias in WKY-ABD was significantly higher compared to non-dilated WKY atria. In WKY-ABD we found a reduction of conduction velocity, similar to that observed in SHR atria, while action potential duration was unchanged. Low-dose caffeine was used to introduce a drop of CV in WKY atria (WKY-caff), quantitatively similar to the one observed after ABD, but no increased arrhythmia susceptibility was observed with caffeine only. In conclusion, CV decrease is not sufficient to promote arrhythmias; enlargement of atrial surface is essential to create a substrate for acute reentry-based arrhythmias.