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1.
Neuroscience Bulletin ; (6): 135-148, 2022.
Article in English | WPRIM | ID: wpr-922667

ABSTRACT

The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.


Subject(s)
Action Potentials , HEK293 Cells , Humans , Protein Kinase C/metabolism , Pyramidal Cells/enzymology , Shab Potassium Channels/genetics
2.
Article in Chinese | WPRIM | ID: wpr-879270

ABSTRACT

Spinal cord stimulation (SCS) for pain is usually implanted as an open loop system using unchanged parameters. To avoid the under and over stimulation caused by lead migration, evoked compound action potentials (ECAP) is used as feedback signal to change the stimulating parameters. This study established a simulation model of ECAP recording to investigate the relationship between ECAP component and dorsal column (DC) fiber recruitment. Finite element model of SCS and multi-compartment model of sensory fiber were coupled to calculate the single fiber action potential (SFAP) caused by single fiber in different spinal cord regions. The synthetized ECAP, superimposition of SFAP, could be considered as an index of DC fiber excitation degree, because the position of crests and amplitude of ECAP corresponds to different fiber diameters. When 10% or less DC fibers were excited, the crests corresponded to fibers with large diameters. When 20% or more DC fibers were excited, ECAP showed a slow conduction crest, which corresponded to fibers with small diameters. The amplitude of this slow conduction crest increased as the stimulating intensity increased while the amplitude of the fast conduction crest almost remained unchanged. Therefore, the simulated ECAP signal in this paper could be used to evaluate the degree of excitation of DC fibers. This SCS-ECAP model may provide theoretical basis for future clinical application of close loop SCS base on ECAP.


Subject(s)
Action Potentials , Computer Simulation , Electric Stimulation , Evoked Potentials , Spinal Cord , Spinal Cord Stimulation
3.
Article in Chinese | WPRIM | ID: wpr-879269

ABSTRACT

As a noninvasive neuromodulation technique, transcranial magnetic stimulation (TMS) is widely used in the clinical treatment of neurological and psychiatric diseases, but the mechanism of its action is still unclear. The purpose of this paper is to investigate the effects of different frequencies of magnetic stimulation (MS) on neuronal excitability and voltage-gated potassium channels in the


Subject(s)
Action Potentials , Animals , Magnetic Phenomena , Mental Disorders , Mice , Neurons , Patch-Clamp Techniques , Potassium Channels, Voltage-Gated
4.
Journal of Biomedical Engineering ; (6): 1081-1086, 2021.
Article in Chinese | WPRIM | ID: wpr-921848

ABSTRACT

In this paper, a new surface electromyography (sEMG) signal decomposition method based on spatial location is proposed for the high-density sEMG signals in dynamic muscle contraction. Firstly, according to the waveform correlation of each muscle motor units (MU) in each channel, the firing times are extracted, and then the firing times are classified by the spatial location of MU. The MU firing trains are finally obtained. The simulation results show that the accuracy rate of a single MU firing train after classification is more than 91.67%. For real sEMG signals, the accuracy rate to find a same MU by the "two source" method is over (88.3 ± 2.1)%. This paper provides a new idea for dynamic sEMG signal decomposition.


Subject(s)
Action Potentials , Computer Simulation , Electromyography , Muscle Contraction , Muscle, Skeletal
5.
Braz. arch. biol. technol ; 64: e21200245, 2021. tab, graf
Article in English | LILACS | ID: biblio-1278434

ABSTRACT

Abstract Current trends in science education recommend the complementary use of virtual and hands-on methods of teaching. In neurobiology, for instance, there is a plethora of virtual laboratories and simulators that can be readily combined with traditional physical labs. Unfortunately, physical laboratories are almost unaffordable for many institutions due to the high cost of equipment. In this paper, we present a simple and low-cost in vivo method for demonstrating some of the basic biophysical properties of neural action potentials. The method involves the following steps: a) dissection of the ventral nerve cord of earthworm; b) electrical stimulation; c) amplification and visualization of the medial and lateral giant fibers' action potentials; and d) recording. The system showed stability, expected amplification, high signal-to-noise ratio, and an estimated total cost of US$ 5.662. We provide guidelines for assembling the system and discus its utility as a teaching alternative for low budget institutions.


Subject(s)
Neurobiology/methods , Action Potentials , Low Cost Technology/economics , Schools
7.
Arq. bras. cardiol ; 114(4): 732-735, Abr. 2020. graf
Article in English, Portuguese | SES-SP, LILACS, SES-SP | ID: biblio-1131189

ABSTRACT

Resumo A Ranolazina (RANO), conhecida na clínica como Ranexa, é um fármaco que previne a arritmia cardíaca através da inibição da corrente de sódio tardia (INaT). Um gradiente de voltagem transmural do canal Nav1.5 encontra-se na parede ventricular esquerda do coração. Assim, investigamos os efeitos da RANO em cardiomiócitos saudáveis e em modelo celular da Síndrome do QT longo tipo 3 (SQTL tipo 3). Usamos células isoladas do endocárdio (ENDO) e do epicárdio (EPI) e um software de medição com detecção de bordas por vídeo e microscopia de fluorescência para monitorar os transientes de cálcio. A RANO (0,1, 1, 10 e 30 uM, a 25OC) em uma série de frequências de estimulação teve impacto pouco significativo sobre ambos os tipos de células, mas a RANO (30uM) a 35OC minimizou o encurtamento dos sarcômeros em ~21% para células do endocárdio. Em seguida, para simular a SQTL tipo 3, as células do ENDO e EPI foram expostas à toxina ATX-II da anêmona do mar, que aumenta a INaT. As arritmias celulares induzidas por ATX-II foram suprimidas com o uso da RANO (30 µM) a 35OC. Com base nesses resultados, podemos concluir que a RANO tem um impacto pouco significativo sobre o encurtamento dos sarcômeros de células saudáveis do ENDO e EPI. Além disso, ela suprime as arritmias induzidas por INaT para níveis semelhantes nas células do ENDO e EPI.


Abstract Ranolazine (RANO) prevents cardiac arrhythmia by blocking the late sodium current (INaL). A transmural gradient of Nav1.5 is found in the left ventricular wall of the heart. Thus, we investigated the effects of RANO in healthy cardiomyocytes and in a cellular model of type 3 long QT syndrome (LQT3). We used isolated endocardium (ENDO) and epicardium (EPI) cells and a video edge detection system and fluorescence microscopy to monitor calcium transients. RANO (0.1, 1, 10 and 30 uM, at 25oC) at a range of pacing frequencies showed a minor impact on both cell types, but RANO at 30uM and 35oC for ENDO cells attenuated sarcomere shortening by~21%. Next, to mimic LQT3, we exposed ENDO and EPI cells to anemone toxin II (ATX-II), which augments INaL. Cellular arrhythmias induced by ATX-II were abrogated by RANO (30 µM) at 35oC. Based on our results we can conclude that RANO has a minor impact on sarcomere shortening of healthy ENDO and EPI cells and it abrogates arrhythmias induced by INaLto a similar level in ENDO and EPI cells.


Subject(s)
Humans , Arrhythmias, Cardiac/drug therapy , Long QT Syndrome , Ranolazine/therapeutic use , Anti-Arrhythmia Agents/therapeutic use , Action Potentials , Cardiac Conduction System Disease
8.
Article in Chinese | WPRIM | ID: wpr-879214

ABSTRACT

The method of directly using speed information and angle information to drive attractors model of grid cells to encode environment has poor anti-interference ability and is not bionic. In response to the problem, this paper proposes a grid field calculation model based on perceived speed and perceived angle. The model has the following characteristics. Firstly, visual stream is decoded to obtain visual speed, and speed cell is modeled and decoded to obtain body speed. Visual speed and body speed are integrated to obtain perceived speed information. Secondly, a one-dimensional circularly connected cell model with excitatory connection is used to simulate the firing mechanism of head direction cells, so that the robot obtains current perception angle information in a biomimetic manner. Finally, the two kinds of perceptual information of speed and angle are combined to realize the driving of grid cell attractors model. The proposed model was experimentally verified. The results showed that this model could realize periodic hexagonal firing field mode of grid cells and precise path integration function. The proposed algorithm may provide a foundation for the research on construction method of robot cognitive map based on hippocampal cognition mechanism.


Subject(s)
Action Potentials , Computer Simulation , Computer Systems , Entorhinal Cortex , Grid Cells , Hippocampus , Models, Neurological
9.
Acta Physiologica Sinica ; (6): 757-764, 2020.
Article in English | WPRIM | ID: wpr-878223

ABSTRACT

The aim of the present paper was to study the role of sodium calcium exchanger (NCX) in the generation of action potentials (APs) in cardiomyocytes during early developmental stage (EDS). The precisely dated embryonic hearts of C57 mice were dissected and enzymatically dissociated to single cells. The changes of APs were recorded by whole-cell patch-clamp technique before and after administration of NCX specific blockers KB-R7943 (5 μmol/L) and SEA0400 (1 μmol/L). The results showed that, both KB-R7943 and SEA0400 had potent negative chronotropic effects on APs of pacemaker-like cells, while such effects were only observed in some ventricular-like cardiomyocytes. The negative chronotropic effect of KB-R7943 on ventricular-like cardiomyocytes was accompanied by shortening of AP duration (APD), whereas such an effect of SEA0400 was paralleled by decrease in velocity of diastolic depolarization (Vdd). From embryonic day 9.5 (E9.5) to E10.5, the negative chronotropic effects of KB-R7943 and SEA0400 on ventricular-like APs of embryonic cardiomyocytes gradually disappeared. These results suggest that, in the short-term development of early embryo, the function of NCX may experience developmental changes as evidenced by different roles of NCX in autorhythmicity and APs generation, indicating that NCX function varies with different conditions of cardiomyocytes.


Subject(s)
Action Potentials , Animals , Calcium/metabolism , Mice , Myocytes, Cardiac/metabolism , Sodium/metabolism , Sodium-Calcium Exchanger , Thiourea/pharmacology
10.
Arq. neuropsiquiatr ; 77(8): 550-554, Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019466

ABSTRACT

ABSTRACT Quantitative electromyography is an important tool to evaluate myopathies, and some difficult-to-treat asthmatic patients may have a subclinical corticosteroid myopathic process, using only inhaled corticosteroid, according to some studies. In this report, diaphragm quantitative electromyography was used to evaluate asthmatic difficult-to-treat patients, comparing them with a control group. Significant differences were obtained in amplitude, duration and size index of motor unit action potentials, with lower parameters in the asthmatic patients, which may indicate a myopathic process.


RESUMO Eletromiografia quantitativa é uma ferramenta importante para a avaliação de miopatias, e alguns pacientes asmáticos de difícil controle podem ter um processo miopático subclínico, mesmo usando apenas corticosteroides inalatórios, de acordo com alguns artigos. Nesse artigo a eletromiografia quantitativa do diafragma foi usada para avaliar os pacientes asmáticos de difícil controle, comparando com um grupo controle. Diferenças significativas nas amplitudes, durações e índices de tamanho dos potenciais de unidades motoras foram encontradas, com parâmetros mais baixos nos pacientes asmáticos, o que pode indicar um processo miopático.


Subject(s)
Humans , Male , Female , Adult , Aged , Young Adult , Asthma/physiopathology , Diaphragm/physiopathology , Electromyography/methods , Reference Values , Asthma/drug therapy , Time Factors , Action Potentials/physiology , Case-Control Studies , Treatment Outcome , Adrenal Cortex Hormones/therapeutic use , Statistics, Nonparametric
11.
Acta cir. bras ; 34(3): e201900304, 2019. tab
Article in English | LILACS | ID: biblio-989064

ABSTRACT

Abstract Purpose: To evaluate if the type of electrode (needle vs. surface) affects the electromyoneurography parameters in rats. Methods: Twenty male rats were anesthetized, then compound muscle action potential were recorded using a Neuropack S1 MEB- 9400©. All animals were submitted to two electroneuromyography analysis: first with surface electrode and then by needle electrode. We evaluated the latency, amplitude, duration and area of the negative peak of the gastrocnemius and cranial tibial muscles. Results: There were no significant differences between the groups in the mean of duration, latency, amplitude or area of the negative peak in gastrocnemius and cranial tibial muscles. Conclusion: The type of electrode does not affect the electroneuromyography parameters.


Subject(s)
Animals , Male , Rats , Action Potentials/physiology , Muscle, Skeletal/physiology , Electrodes , Electromyography/instrumentation , Neural Conduction/physiology , Reaction Time , Rats, Wistar
12.
Article in Korean | WPRIM | ID: wpr-766750

ABSTRACT

BACKGROUND: The accurate grading of chemotherapy-induced peripheral neuropathy (CIPN) represents an unsolved issue. This study evaluated usefulness of the reduced version of Total Neuropathy Score TNS (TNSr) and the correlation of this scale with various electrophysiological parameters. METHODS: Neuropathic symptoms and quality of life were assessed using the neuropathy symptom scale and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity (FACT/GOG-NTX) scale. A detailed neurologic examination, nerve conduction study (NCS), and the current perception threshold (CPT) were also performed. The TNSr score was calculated by a single examiner. We divided the patients with small fiber neuropathy and large fiber neuropathy and compared each variable between groups. Also, we analyzed correlations of the TNSr score with various parameters (NCS data, CPT score, and neuropathy symptom scales). RESULTS: Of 30 recruited patients, 16 (53%) had large fiber neuropathy, and the other 14 (47%) had small fiber neuropathy. Patients with large fiber neuropathy had a lower sural sensory nerve action potential (SNAP) (p=0.000), lower peroneal compound muscle action potential (CMAP) (p=0.002), higher National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, NTC) sensory grade (p=0.029) and higher TNSr score (p=0.000). There were no differences in any domain of the FACT/G, neuropathy symptom scale, or FACT/GOG-NTX between the two groups. The TNSr score was most significantly correlated with the sural SNAP (p=0.000), NTC-sensory grade (p=0.000), neuropathy symptom scale (p=0.001), FACT/GOG-NTX score (p=0.009), and pin score (p=0.002). CONCLUSIONS: The TNSr score is correlated with sensory peripheral neurotoxicity and also present the symptom severity in CIPN.


Subject(s)
Action Potentials , Breast Neoplasms , Breast , Erythromelalgia , Humans , Neural Conduction , Neurologic Examination , Neurologic Manifestations , Peripheral Nervous System Diseases , Polyneuropathies , Quality of Life
13.
Chinese Medical Journal ; (24): 542-550, 2019.
Article in English | WPRIM | ID: wpr-774801

ABSTRACT

BACKGROUND@#Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily.@*METHODS@#A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1, 2012 and February 28, 2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude.@*RESULTS@#The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1% (46/85) in the ALS group, and the results of different nerves were 54.1% (46/85) of the accessory nerve, 8.2% (7/85) of the ulnar nerve and 0% (0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100% (41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave.@*CONCLUSIONS@#Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases.


Subject(s)
Action Potentials , Physiology , Adult , Aged , Amyotrophic Lateral Sclerosis , Therapeutics , Electric Stimulation Therapy , Electromyography , Female , Humans , Male , Median Nerve , Physiology , Middle Aged , Motor Neurons , Physiology , Muscle, Skeletal , Physiology , Myasthenia Gravis , Therapeutics , Retrospective Studies , Ulnar Nerve , Physiology
14.
Article in Chinese | WPRIM | ID: wpr-774223

ABSTRACT

Deep brain stimulation (DBS), which usually utilizes high frequency stimulation (HFS) of electrical pulses, is effective for treating many brain disorders in clinic. Studying the dynamic response of downstream neurons to HFS and its time relationship with stimulus pulses can reveal important mechanisms of DBS and advance the development of new stimulation modes (e.g., closed-loop DBS). To exhibit the dynamic neuronal firing and its relationship with stimuli, we designed a two-dimensional raster plot to visualize neuronal activity during HFS (especially in the initial stage of HFS). Additionally, the influence of plot resolution on the visualization effect was investigated. The method was then validated by investigating the neuronal responses to the axonal HFS in the hippocampal CA1 region of rats. Results show that the new design of raster plot is able to illustrate the dynamics of indexes (such as phase-locked relationship and latency) of single unit activity (i.e., spikes) during periodic pulse stimulations. Furthermore, the plots can intuitively show changes of neuronal firing from the baseline before stimulation to the onset dynamics during stimulation, as well as other information including the silent period of spikes immediately following the end of HFS. In addition, by adjusting resolution, the raster plot can be adapted to a large range of firing rates for clear illustration of neuronal activity. The new raster plot can illustrate more information with a clearer image than a regular raster plot, and thereby provides a useful tool for studying neuronal behaviors during high-frequency stimulations in brain.


Subject(s)
Action Potentials , Animals , Axons , Physiology , CA1 Region, Hippocampal , Physiology , Deep Brain Stimulation , Neurons , Physiology , Rats
15.
Article in Chinese | WPRIM | ID: wpr-776523

ABSTRACT

OBJECTIVE@#To quantitatively investigate the effects of Ringer's solution with different concentrations of alcohol (1%~80%) on biphasic compound action potentials (AP) from frog sciatic nerve trunk, and their recoveries from alcohol effects.@*METHODS@#Individual segments of frog sciatic nerve trunk with a length of 6 to 8 cm were prepared. Ringer's solution with different concentrations of alcohol (0%, 1%, 2%, 4%, 8%, 16%, 32%, 48%, 64% and 80%) was applied onto the segment of the trunk between the stimulus and ground electrodes via an agent reservoir which was newly armed in a nerve trunk shielded chamber for 5 minutes. The nerve trunk was respectively electro-stimulated to generate the biphasic compound AP which was recorded using the experimental system of BL-420F. This was followed by 5 times washout plus 5 min administration with Ringer's solution before recovery recording of AP.@*RESULTS@#Compared to normal Ringer's solution, Ringer's solution with alcohol at ≤4% did not have dramatic impacts on the AP amplitude and conduction velocity, while Ringer's solution with alcohol at ≥8% there was significant decrease in these two parameters. Ringer's solution with alcohol at the conentrations of 16%, 32% and ≥48% could prevent a small proportion (30%), a large proportion (90%) and all (100%) of sciatic nerve trunks, respectively, from generating AP. Washout with normal Ringer's solution after alcohol application at the concentration of ≤32%, AP could totally recover to normal status. While alcohol at the concentration of 48%, 64% and 80%, the probabilities to regenerate APs were 90%, 40% and 0%, and the AP amplitudes were decreased to 60%, 36% and 0%, respectively. After washout, AP conduction velocity showed no difference with alcohol at the concentration of ≤8% when compared with that before washout, while it could not be recovered to normal under alcohol at ≥16%.@*CONCLUSION@#Ringer's solution with different concentrations of alcohol exerts different effects on biphasic compound AP amplitude and conduction velocity. Hopefully, our findings could be helpful for the alcoholic usage and its recovery from alcoholic damage.


Subject(s)
Action Potentials , Animals , Anura , Ethanol , Pharmacology , Ringer's Solution , Pharmacology , Sciatic Nerve
16.
Article in Korean | WPRIM | ID: wpr-758523

ABSTRACT

BACKGROUND AND OBJECTIVES: Laryngeal electromyography (LEMG) is valuable to evaluate the innervation status of the laryngeal muscles and the prognosis of vocal fold paralysis (VFP). However, there is a lack of agreement on quantitative interpretation of LEMG. The aim of this study is to measure the motor unit action potentials (MUAP) quantitatively in order to find cut-off values of amplitude, duration, phase for unilateral vocal fold paralysis patients. MATERIALS AND METHOD: Retrospective chart review was performed for the unilateral VFP patients who underwent LEMG from March 2016 to May 2018. Patient's demography, cause of VFP, vocal cord mobility, and LEMG finding were analyzed. The difference between normal and paralyzed vocal folds and cut-off values of duration, amplitude, and phase in MUAP were evaluated. RESULTS: Thirty-six patients were enrolled in this study. Paralyzed vocal fold had significantly longer duration (p=0.021), lower amplitude (p=0.000), and smaller phase (p=0.012) than the normal. The cut-off values of duration, amplitude, and phase in MUAP for unilateral VFP were 5.15 ms, 68.35 µV, and 1.85 respectively. CONCLUSION: An analysis of MUAP successfully provided quantitative differences between normal and paralyzed vocal folds. But, additional research is needed to get more available cut-off value which is helpful to evaluate the status of laryngeal innervations.


Subject(s)
Action Potentials , Demography , Electromyography , Humans , Laryngeal Muscles , Methods , Paralysis , Prognosis , Retrospective Studies , Vocal Cord Paralysis , Vocal Cords
17.
Article in English | WPRIM | ID: wpr-761815

ABSTRACT

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. β-Amyloid (Aβ) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aβ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aβ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aβ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A₁ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aβ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A₁R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.


Subject(s)
Action Potentials , Adenosine , Alzheimer Disease , Fires , Ibotenic Acid , Membranes , Neurons , Neuroprotection , Neuroprotective Agents , Patch-Clamp Techniques , Pyramidal Cells
18.
Article in English | WPRIM | ID: wpr-761797

ABSTRACT

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with IC₅₀ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect I(Na), I(Ks) or I(K1), but decreased I(hERG) in a dose-dependent manner (IC₅₀: 6.53 µM). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to 3 µM, but it at 10 µM induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.


Subject(s)
Action Potentials , Animals , Antineoplastic Agents , Aurora Kinases , Cardiotoxicity , Cell Division , Cell Line , Humans , In Vitro Techniques , Ion Channels , Muscle Cells , Myocardial Contraction , Myocytes, Cardiac , Phosphotransferases , Rats , Relaxation
19.
Article | WPRIM | ID: wpr-764218

ABSTRACT

BACKGROUND AND OBJECTIVES: The present study aims to investigate whether the cochlear implant electrode array design affects the electrophysiological and psychophysical measures. SUBJECTS AND METHODS: Eighty five ears were used as data in this retrospective study. They were divided into two groups by the electrode array design: lateral wall type (LW) and perimodiolar type (PM). The electrode site was divided into three regions (basal, medial, apical). The evoked compound action potential (ECAP) threshold, T level, C level, dynamic range (DR), and aided air conduction threshold were measured. RESULTS: The ECAP threshold was lower for the PM than for the LW, and decreased as the electrode site was closer to the apical region. The T level was lower for the PM than for the LW, and was lower on the apical region than on the other regions. The C level on the basal region was lower for the PM than for the LW whereas the C level was lower on the apical region than on the other regions. The DRs on the apical region was greater for the PM than for the LW whereas the DR was narrower on the apical region than on the other regions. The aided air conduction threshold was not different for the electrode design and frequency. CONCLUSIONS: The current study would support the advantages of the PM over the LW in that the PM had the lower current level and greater DR, which could result in more localized neural stimulation and reduced power consumption.


Subject(s)
Action Potentials , Cochlear Implants , Ear , Electrodes , Retrospective Studies
20.
Experimental Neurobiology ; : 320-328, 2019.
Article in English | WPRIM | ID: wpr-763772

ABSTRACT

The basolateral amygdala (BLA) receives dense projections from cholinergic neurons of the basal forebrain. Acetylcholine can contributes to amygdala-dependent behaviors: formation and extinction of fear memory and appetitive instrumental learning. However, the cholinergic mechanism at the circuit level has not been defined yet. We demonstrated that cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons exhibits a retrograde form of short-term synaptic inhibition, depolarization-induced suppression of inhibition (DSI). Activation of nicotinic receptors was sufficient to evoke action potentials in cholecystokinin (CCK)-positive inhibitory neurons, which strongly inhibit pyramidal neurons through their perisomatic synapses. Our cell type-specific monosynaptic retrograde tracing also revealed that CCK neurons are innervated by basal forebrain cholinergic neurons. Therefore, our data indicated that CCK inhibitory neurons mediate the cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons.


Subject(s)
Acetylcholine , Action Potentials , Basal Forebrain , Basolateral Nuclear Complex , Cholecystokinin , Cholinergic Neurons , Conditioning, Operant , Iontophoresis , Memory , Neurons , Pyramidal Cells , Receptors, Nicotinic , Synapses
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