Period Of Depolarization Research Articles

Correlation of the Left Ventricular Systolic Dysfunction and Ventricular Depolarization in a Post-Infarction Model of Chronic Heart Failure.

The body surface potential mapping of the heart during the period of ventricular depolarization and the inotropic function of the ventricles were studied in rats under conditions of a translational model of post-infarction chronic heart failure developed by us. We revealed a statistically significant (p<0.001) correlation between the left-ventricular ejection fraction and the values of the maximum positive and negative extrema of the cardioelectric field on the body surface of rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction. The calculated linear regression equations have high predictive efficiency, which makes it possible to use the amplitude characteristics of the heart cardioelectric field as a marker of the development of chronic heart failure.

Electric Field of the Heart on the Thorax Surface in Highly Trained Athletes during Initial Ventricular Activity

The article is focused on the study of the electrical remodeling of the “sports heart” using multichannel ECG mapping to make a more detailed and informative analysis of the excitation of the myocardium remodeled by sport activity. The study of the heart electrical activity was carried out from 64 unipolar electrodes on the thorax surface synchronously with standard limb leads in highly trained cross-country skiers (n = 15) and young non-trained men (n = 19) at rest. The amplitude-temporal and spatiotemporal characteristics of the electric field of the heart were measured. By the typical distribution of areas of the negative and positive cardiac potentials the durations of depolarization and its individual phases were estimated. ECGII was used to determine the duration of the R-R, PQ (PR), QRS, QT, QTc intervals; in the unipolar lead V5 the R-wave peak time (RWPTV5) was measured. In athletes, the duration of PQII, QTII, QTcII, RWPTV5 intervals were statistically significantly longer than in non-trained men. Analysis of the electrical field of the heart showed a difference in the ratio of the phases of ventricular depolarization in athletes and non-trained individuals at rest. The onset of ventricular depolarization and the first inversion of cardiac potential in athletes were significantly earlier than in non-trained people, while the completion and total duration of the period of ventricular depolarization did not differ. In skiers, the duration of the first inversion was significantly longer than in non-trained individuals; a tendency to shortening of the second period of stable location of potentials on the thorax surface was also shown. The use of surface ECG mapping made it possible to reveal differences in the spatiotemporal organization of heart ventricular depolarization between cross-country skiers and non-trained men at rest. The results of the study may be useful in the analysis of the electrical remodeling of the heart in athletes training the physical quality of endurance.

ELECTRICAL ACTIVITY OF THE HUMAN HEART DURING THE PERIOD OF VENTRICULAR DEPOLARIZATION UNDER ACUTE NORMOBARIC HYPOXIA

Background. The effect of acute hypoxia on the human heart leads to deterioration of the heart function, this is reflected in an increase of the heterogeneity of the depolarization process, which is difficult to reveal when using a traditional ECG.&#x0D; Purpose. To investigate the electrical activity of the heart during the ventricular depolarization on the thorax surface under the exposure of acute normobaric hypoxia using multichannel ECG mapping.&#x0D; Material and methods. The electrical activity of the heart in apparently healthy young men (20±1 years) was studied during ventricular depolarization under exposure of acute normobaric hypoxia using cardioelectrotopography. Unipolar ECGs were recorded from 64 electrodes on the surface of the chest, simultaneously with bipolar ECGs in limb leads and the amplitudes of R and S waves from the surface electrodes localized in positions V1 and V5 of the traditional ECG were evaluated.&#x0D; Results. It was revealed that during hypoxia, in comparison with the initial state, the pattern of distribution and the spatio-temporal dynamics of positive and negative cardiac potentials reflecting the sequence of myocardial activation on the torso surface did not change significantly and were typical for the period of ventricular depolarization of the healthy person. A decrease in the amplitudes of the maximum extrema of cardiac electric potentials, the amplitudes of the SV1 and RV5 waves at hypoxic exposure was revealed: the amplitude of the maximum decreased from 1.88±0.58 mV in the initial state to 1.83±0.55 mV at hypoxia, the minimum – from -2.08±0.76 mV to -1.85±0.73 mV, the SV1 wave from -1.28±0.25 mV to -1.17±0.18 mV, RV5 wave from 1.21±0.25 mV to 1.05±0.29 mV, respectively, while the duration of ventricular depolarization did not change statistically significantly.&#x0D; Conclusion. Under hypoxic exposure, the examined persons showed a significant decrease in the amplitudes of the maximum extrema of the electric field of the heart, a direct correlation between changes in the amplitudes of the positive extremum and the RV5 wave, with practically unchanged duration of ventricular depolarization and dynamics of the distribution of cardioelectric potentials.

Body surface potential mapping in rats with stress-induce arterial hypertension

Studies on experimental animals allow us to approach the understanding of the mechanisms of changes in the electrical activity of the heart during morphofunctional rearrangements that occur as a result of the development of arterial hypertension (AH). Aim of the study was to investigate body surface potential mapping in young ISIAH rats with genetically determined stress-induced AH during ventricular depolarization. Material and methods. The study was carried out on 3-month-old ISIAH males ( n = 10) weighing 250–300 g. Body surface potential mapping was performed using 64 electrodes evenly distributed around the chest of the animal. Results. Significantly higher systolic blood pressure was shown in ISIAH rats compared to Wistar rats (203 ± 14 and 125 ± 5 mm Hg, respectively), as well as heart relative mass, thickness of the left ventricle, right ventricle, and interventricular septum were significantly higher compared to Wistar. During the period of ventricular depolarization, a shift of the zone of negative cardiopotentials to the left-lateral region of the chest is shown in the period corresponding to the time the positive extremum reaches its maximum value in ISIAH rats compared to Wistar. An earlier time of formation, a significantly longer time to achieve the first and second inversion of cardiopotentials, a later time for the positive and negative extrema to reach their maximum values, a greater amplitude of the absolute value of the negative extremum, and a significantly longer total ventricular duration in ISIAH rats compared to Wistar rats were shown. Conclusions. The study give perspective to the use of body surface potential mapping for diagnosing the initial stages of the formation of myocardial hypertrophy in AH.

The peak force-resting membrane potential relationships of mouse fast- and slow-twitch muscle.

We endeavored to understand the factors determining the peak force-resting membrane potential (EM) relationships of isolated slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles from mice (25°C), especially in relation to fatigue. Interrelationships between intracellular K+ activity ([Formula: see text]), extracellular K+ concentration ([K+]o), resting EM, action potentials, and force were studied. The large resting EM variation was mainly due to the variability of [Formula: see text]. Action potential overshoot-resting EM relationships determined at 4 and 8-10 mM [K+]o after short (<5 min) and prolonged (>50 min) depolarization periods revealed a constant overshoot from -90 to -70 mV providing a safety margin. Overshoot decline with depolarization beyond -70 mV was less after short than prolonged depolarization. Inexcitable fibers occurred only with prolonged depolarization. The overshoot decline during action potential trains (2 s) exceeded that during short depolarizations. Concomitant lower extracellular [Na+] and raised [K+]o depressed the overshoot in an additive manner and peak force in a synergistic manner. Raised [K+]o-induced force loss was exacerbated with transverse wire versus parallel plate stimulation in soleus, implicating action potential propagation failure in the surface membrane. Increasing stimulus pulse parameters restored tetanic force at 9-10 mM [K+]o in soleus but not EDL, indicative of action potential failure within trains. The peak tetanic force-resting EM relationships (determined with resting EM from deeper rather than surface fibers) were dynamic and showed pronounced force depression over -69 to -60 mV in both muscle types, implicating that such depolarization contributes to fatigue. The K+-Na+ interaction shifted this relationship toward less depolarized potentials, suggesting that the combined ionic effect is physiologically important during fatigue.

Dynamics of the cardioelectric field of rats under chronic exposure to doxorubicin during atrial depolarization

The aim of the work is non-invasive identification of the features of the initial atrial activity by the dynamics of the cardioelectric field on the surface of the chest of experimental animals under chronic exposure to doxorubicin. Materials and methods . The distribution and dynamics of changes in cardioelectric potentials on the surface of the chest of rats under chronic exposure to doxorubicin during the period of initial atrial activity were investigated. Doxorubicin was administered intraperitoneally 1.5 mg/kg once a week for a month. The cumulative dose was 6 mg/kg animal weight. Results . It has been shown that chronic exposure to doxysubicin leads to changes in the positional dynamics of positive and negative cardiopotentials cardioelectric field of heart on the chest surface during the ascending and descending P-wave on the ECG in the II limb leads. It is observed significantly earlier the beginning of cardioelectric field formation, characteristic of atrial depolarization, on the body surface, the beginning, the peak and the end of the P-wave on the ECG in the II limb leads compared to the initial state. Conclusion . Chronic exposure to doxorubicin causes significant changes in the initial atrial activity, which leads to a significant change in the corresponding period of atrial depolarization in the dynamics of the cardioelectric field on the surface of the thorax of animals.

Paired Feed-Forward Excitation With Delayed Inhibition Allows High Frequency Computations Across Brain Regions.

The transmission of high frequency temporal information across brain regions is critical to perception, but the mechanisms underlying such transmission remain unclear. Long-range projection patterns across brain areas are often comprised of paired feed-forward excitation followed closely by delayed inhibition, including the thalamic triad synapse, thalamic projections to cortex, and projections within the hippocampus. Previous studies have shown that these joint projections produce a shortened period of depolarization, sharpening the timing window over which the postsynaptic neuron can fire. Here we show that these projections can facilitate the transmission of high frequency computations even at frequencies that are highly filtered by neuronal membranes. This temporal facilitation occurred over a range of synaptic parameter values, including variations in synaptic strength, synaptic time constants, short-term synaptic depression, and the delay between excitation and inhibition. Further, these projections can coordinate computations across multiple network levels, even amid ongoing local activity. We suggest that paired feed-forward excitation and inhibition provide a hybrid signal—carrying both a value and a clock-like trigger—to allow circuits to be responsive to input whenever it arrives.

Cannabidiol Selectively Binds to the Voltage-Gated Sodium Channel Nav1.4 in Its Slow-Inactivated State and Inhibits Sodium Current.

Cannabidiol (CBD), one of the cannabinoids from the cannabis plant, can relieve the myotonia resulting from sodium channelopathy, which manifests as repetitive discharges of muscle membrane. We investigated the binding kinetics of CBD to Nav1.4 channels on the muscle membrane. The binding affinity of CBD to the channel was evaluated using whole-cell recording. The CDOCKER program was employed to model CBD docking onto the Nav1.4 channel to determine its binding sites. Our results revealed no differential inhibition of sodium current by CBD when the channels were in activation or fast inactivation status. However, differential inhibition was observed with a dose-dependent manner after a prolonged period of depolarization, leaving the channel in a slow-inactivated state. Moreover, CBD binds selectively to the slow-inactivated state with a significantly faster binding kinetics (>64,000 M−1 s−1) and a higher affinity (Kd of fast inactivation vs. slow-inactivation: >117.42 μM vs. 51.48 μM), compared to the fast inactivation state. Five proposed CBD binding sites in a bundle crossing region of the Nav1.4 channels pore was identified as Val793, Leu794, Phe797, and Cys759 in domain I/S6, and Ile1279 in domain II/S6. Our findings imply that CBD favorably binds to the Nav1.4 channel in its slow-inactivated state.

The cardiac electric field in psychrophilic and thermophilic fish during atrial depolarization

In psychrophilic and thermophilic fish, significant differences were revealed under an optimal body temperature in the heart rate, initial atrial activity duration and descending slope of the P II wave. Differences were also detected in atrial electric activity during the initial and final periods of depolarization, reflecting different localization of the initial excitation area and the movement of the depolarization front toward the atrioventricular border.

Neurotransmitter Release Can Be Stabilized by a Mechanism That Prevents Voltage Changes Near the End of Action Potentials from Affecting Calcium Currents.

The shape of presynaptic action potentials (APs), particularly the falling phase, affects calcium entry and small changes in calcium influx can produce large changes in postsynaptic responses. We hypothesized that afterpotentials, which often follow APs, affect calcium entry and neurotransmitter release. We tested this in calyx of Held nerve terminals, which allow simultaneous recording of presynaptic calcium currents and postsynaptic responses. Surprisingly, presynaptic afterpotentials did not alter calcium current or neurotransmitter release. We show that the AP falling phase causes afterpotential-induced changes in electrical driving force and calcium channel gating to cancel each other out. This mechanism regulates calcium entry at the end of APs and therefore stabilizes synaptic transmission. This also stabilizes responses when the presynaptic resting potential changes.

MPS 08-04 The association between ST interval and blood pressure in a general population of Korea

Objective: To evaluate the association of PR interval, QRS duration, and ST interval with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a general population of Korea. Design and Method: We conducted a cross-sectional analysis from the data of Cardiovascular and Metabolic diseases Etiology Research Center, an ongoing cohort of general population. Total 587 men and 1065 women were separately analyzed. PR interval, QRS duration and QT interval was obtained from electrocardiogram; ST interval was calculated by subtracting QRS duration from QT interval. Resting blood pressure was measured using an automatic sphygmomanometer. Linear regression analysis was used to obtain the estimates of each SBP and DBP with each PR interval, QRS duration, and ST interval, adjusting for age, body mass index, heart rate, triglyceride, high density lipoprotein cholesterol, smoking behavior, insulin, and diagnosis of hypertension or diabetes. Results: One beat per minute increase of resting heart rate was significantly associated with high DBP in both sexes, and low SBP in women. In men, the estimates (p value) for SBP (mmHg) with 10 millisecond increase of each PR interval, QRS duration, and ST interval was −0.013 (0.86), 0.467 (0.10), and 0.303 (0.01), respectively. The corresponding estimates (p value) was −0.045 (0.41), −0.255 (0.20), and −0.356 (<.001) for DBP (mmHg). In women, the estimates (p value) was 0.020 (0.61), 0.073 (0.37), and 0.053 (0.01) for SBP, and −0.017 (0.53), −0.053 (0.34), and −0.041 (0.004) for DBP. Conclusions: Beyond the three components of a heart rhythm, ST interval was significantly associated with high SBP and low DBP. This finding suggests that period of ventricle depolarization is associated with blood pressure.

Mutations in the Voltage Sensors of Domains I and II of Nav1.5 that are Associated with Arrhythmias and Dilated Cardiomyopathy Generate Gating Pore Currents.

Voltage gated sodium channels (Nav) are transmembrane proteins responsible for action potential initiation. Mutations mainly located in the voltage sensor domain (VSD) of Nav1.5, the cardiac sodium channel, have been associated with the development of arrhythmias combined with dilated cardiomyopathy. Gating pore currents have been observed with three unrelated mutations associated with similar clinical phenotypes. However, gating pores have never been associated with mutations outside the first domain of Nav1.5. The aim of this study was to explore the possibility that gating pore currents might be caused by the Nav1.5 R225P and R814W mutations (R3, S4 in DI and DII, respectively), which are associated with rhythm disturbances and dilated cardiomyopathy. Nav1.5 WT and mutant channels were transiently expressed in tsA201 cells. The biophysical properties of the alpha pore currents and the presence of gating pore currents were investigated using the patch-clamp technique. We confirmed the previously reported gain of function of the alpha pores of the mutant channels, which mainly consisted of increased window currents mostly caused by shifts in the voltage dependence of activation. We also observed gating pore currents associated with the R225P and R814W mutations. This novel permeation pathway was open under depolarized conditions and remained temporarily open at hyperpolarized potentials after depolarization periods. Gating pore currents could represent a molecular basis for the development of uncommon electrical abnormalities and changes in cardiac morphology. We propose that this biophysical defect be routinely evaluated in the case of Nav1.5 mutations on the VSD.

Physiological parameters as a tool in the diagnosis of fibromyalgia syndrome in females: A preliminary study

AimsAlthough fibromyalgia (FM) syndrome is associated with many symptoms, there is as yet no specific finding or laboratory test diagnostic of this syndrome. The physical examination and laboratory tests may be helpful in figuring out this syndrome. Materials and methodsThe heart rate, respiration rate, body temperature (TEMP), height, body weight, hemoglobin level, erythrocyte sedimentation rate, white blood cell count, platelet count (PLT), rheumatoid factor and C-reactive protein levels and electrocardiograms (ECG) of FM patients were compared with those of control individuals. In addition, the predictive value of these tests was evaluated via receiver operating characteristic (ROC) analysis. Key findingsThe results showed that the TEMP and the PLT were higher in the FM group compared with the control group. Also, ST heights in ECGs which corresponds to a period of ventricle systolic depolarization, showed evidence of a difference between the FM and the control groups. There was no difference observed in terms of the other parameters. According to the ROC analysis, PLT, TEMP and ST height have predictive capacities in FM. SignificanceChanges in hormonal factors, peripheral blood circulation, autonomous system activity disorders, inflammatory incidents, etc., may explain the increased TEMP in the FM patients. The high PLT level may signify a thromboproliferation or a possible compensation caused by a PLT functional disorder. ST depression in FM patients may interrelate with coronary pathology. Elucidating the pathophysiology underlying the increases in TEMP and PLT and the decreases in ST height may help to explain the etiology of FM.

Quantitative study of electric conduction in mineral oil by time domain and frequency domain measurement

Polarization and depolarization current measurement is a non-destructive testing method to study the dielectric properties of insulating materials. Two types of mineral oils with different aging times have been studied using both time domain and frequency domain methods separately. In this paper, a novel approach to understanding the correlation between the electric conduction in time domain and frequency domain has been proposed. When the charge carriers drift to the electrodes, they may be blocked and accumulated near the electrode. The amount of charge in the vicinity of electrode has been estimated. In the depolarization period, these charge layers will return to the bulk resulting in a depolarization current. In this paper, an analytical solution to the time dependence of the depolarization current has been developed and used to fit the experimental results. The field and temperature dependence of the polarization and depolarization current have been used to study the characteristics of charge carriers in mineral oil. The calculated conductivity has been used to simulate the frequency response in mineral oil and the simulating results have been compared with the experimental data.

Synaptic dynamics and neuronal network connectivity are reflected in the distribution of times in Up states.

The dynamics of neuronal networks connected by synaptic dynamics can sustain long periods of depolarization that can last for hundreds of milliseconds such as Up states recorded during sleep or anesthesia. Yet the underlying mechanism driving these periods remain unclear. We show here within a mean-field model that the residence time of the neuronal membrane potential in cortical Up states does not follow a Poissonian law, but presents several peaks. Furthermore, the present modeling approach allows extracting some information about the neuronal network connectivity from the time distribution histogram. Based on a synaptic-depression model, we find that these peaks, that can be observed in histograms of patch-clamp recordings are not artifacts of electrophysiological measurements, but rather are an inherent property of the network dynamics. Analysis of the equations reveals a stable focus located close to the unstable limit cycle, delimiting a region that defines the Up state. The model further shows that the peaks observed in the Up state time distribution are due to winding around the focus before escaping from the basin of attraction. Finally, we use in vivo recordings of intracellular membrane potential and we recover from the peak distribution, some information about the network connectivity. We conclude that it is possible to recover the network connectivity from the distribution of times that the neuronal membrane voltage spends in Up states.

TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through p62/SQSTM1 phosphorylation

Selective autophagy adaptor proteins, including p62/SQSTM1, play pivotal roles in the targeted degradation of ubiquitinated proteins or organelles through the autophagy-lysosome system. However, how autophagy adaptors promote the autophagosomal engulfment of selected substrates is poorly understood. Here, we show that p62 phosphorylation at S403 is required for the efficient autophagosomal engulfment of polyubiquitinated mitochondria during Parkin-dependent mitophagy. p62 is able to interact with Parkin-recruited mitochondria without S403 phosphorylation under mitophagy-inducing conditions, but those mitochondria are not enclosed by autophagosomes. Intriguingly, the S403 phosphorylation occurs only in the early period of mitochondrial depolarization. Optineurin and TANK-binding kinase 1 (TBK1) are transiently recruited to the polyubiquitinated mitochondria, and the activated TBK1 phosphorylates p62 at S403. TBK1 inhibitor, BX795, prevents the p62-mediated autophagosomal engulfment of Parkin-recruited mitochondria. Our results suggest that TBK1-mediated S403 phosphorylation regulates the efficient autophagosomal engulfment of ubiquitinated mitochondria as an immediate response to the mitochondrial depolarization.

Mechanisms of QRS voltage changes on ECG of healthy subjects during the exercise test

Electrocardiography is the most commonly used technique for detection stress-induced myocardial ischemia. However, the sensitivity of ECG-criteria is not high. One of the major problem is the difficulty in differentiating ECG changes caused by various factors. The aim of this study was to evaluate the dependence of the QRS voltage changes during exercise on parameters of central hemodynamics, gender particularities and to reveal mechanisms causing these changes. To eliminate the effect of changes in cardiomyocytes transmembrane potentials under the influence of the neurotransmitters of the autonomic nervous system during stepwise increasing exercises and/or due to a lack of ATP results from inadequate myocardial blood flow only healthy subjects not older than 35 years were included in the study (7 men and 7 women) and only periods of ventricular depolarization (QRS complex on the ECG) were included in the analysis. We compared the changes of QRS waves during exercise sessions with two upper and one lower limbs in both men and women. The exercise load was twice bigger in exercise with one leg relative to exercise with two arms. Responses of heart rate and systolic arterial pressure were similar. Amplitude of S-wave in left chest leads significantly increased in both sessions without significant difference between augmentations in the sessions and in groups of men and women. Significant relationship between the S wave augmentation and the peak systolic arterial pressure were revealed. Furthermore, the QRS changes during the exercise with vertical and a horizontal torso position were compared to assess the impact of diastolic arterial pressure and displacement of the diaphragm and heart rotation due to increase of abdominal pressure during the last steps of exercise. The obtained results allow us to exclude the impact of the heart position and size changes, as well as the exercise load on S-wave changes and make a conclusion about the dependence of this parameter on the value of systolic blood pressure.

Cardiac Memory: A Rare Cause of Postoperative Deep T Wave Inversions

Cardiac memory (CM) is a phenomenon of electrical remodeling seen after periods of altered ventricular conduction. In this unique finding, the T wave direction during “memory”, or periods after altered depolarization, is similar to that of the QRS complex during periods of abnormal depolarization. The T wave abnormalities are commonly seen after ventricular pacing, but can also been seen with intermittent left bundle branch block (LBBB). We present a case of a high-risk elderly male who developed deep T wave inversions (TWIs) postoperatively. While ischemia is highest on the differential diagnosis in such a case, our patient was asymptomatic with negative serial troponins. Also, our patient developed the deep TWIs in the setting of an intermittent LBBB. The diagnosis of CM was made after thorough evaluation of other causes of TWIs. It is important for clinicians to be aware of CM, as it is often misinterpreted as ischemia and early diagnosis can help prevent unnecessary invasive workup. J Med Cases. 2015;6(11):520-522 doi: https://doi.org/10.14740/jmc2333w

Spatiotemporal characteristics of the heart electrical field in the period of ventricular depolarization in athletes training endurance and strength

As a result of haemodynamic and structural changes occurring in athletes' heart under the influence of systematic physical loads, myocardial electrical activity changes that is reflected on the electric field being formed on the body surface. The heart electrical activity during ventricular depolarization at rest has been investigated in the highly skilled athletes who train to develop physical characteristics--endurance and strength by a method of electrocardiotopography. In the investigated sportsmen under uniformity of the character of the movement of positive and negative cardioelectric potential zones and localization of extrema, and general depolarization duration, the significant distinctions of: 1) amplitude of the maximum negative extremum, 2) the time of the beginning and end of the first inversion, 3) duration of the second inversion, the initial stage and the stability period between inversions, 4) the relative location of the zones of positive and negative cardiopotentials were revealed.

Supervised learning with complex spikes and spike-timing-dependent plasticity.

One distinctive feature of Purkinje cells is that they have two types of discharge: in addition to simple spikes they fire complex spikes in response to input from the climbing fibers. These complex spikes have an initial rapid burst of spikes and spikelets followed by a sustained depolarization; in some models of cerebellar function this climbing fiber input supervises learning in Purkinje cells. On the other hand, synaptic plasticity is often thought to rely on the timing of pre-synaptic and post-synaptic spikes. It is suggested here that the period of depolarization following a complex spike, combined with a simple spike-timing-dependent plasticity rule, gives a mechanism for the climbing fiber to supervise learning in the Purkinje cell. This proposal is illustrated using a simple simulation in which it is seen that the climbing fiber succeeds in supervising the learning.