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1.
We investigated whether in the sinoatrial node (SAN) there are two different pacemaker mechanisms and whether either one can maintain spontaneous discharge. These questions were studied by means of an electrophysiological technique and of blockers of different diastolic currents in rabbit and guinea pig isolated SAN. In SAN subsidiary pacemakers of both species, Cs(+) (5-10 mM) or high [K(+)](o) (10-12 mM) decreased the maximum diastolic potential, abolished diastolic depolarization (DD) at polarized levels (subsidiary DD), unmasked a U-shaped dominant DD at depolarized levels, but did not stop the SAN. In rabbit SAN, E4031 (1 microM) and d-sotalol (100 microM) did not stop discharge, but did so after block of subsidiary DD by high [K(+)](o) or Cs(+). In guinea pig SAN, in Tyrode solution E4031, d-sotalol or indapamide (100 microM) did not stop SAN discharge. In the presence of Cs(+) or high [K(+)](o) indapamide (but not E4031 or d-sotalol) stopped the SAN. Ba(2+) (1-5 mM) led to stoppage of discharge both in Tyrode solution and in high [K(+)](o) or Cs(+). Depolarization by blockers of DD unmasked sinusoidal fluctuations, which during recovery were responsible for resumption of discharge. We conclude that in rabbit and guinea pig SAN, two different pacemaker mechanisms (Cs(+)- and K(+)-sensitive subsidiary DD, and Cs(+)- and K(+)-insensitive dominant DD) can independently sustain discharge, but block of both mechanisms leads to quiescence. Abolition of dominant DD by blockers of I(K) is consistent with a decay of I(K) as the dominant pacemaking mechanism, I(Kr) being more important in rabbit and I(Ks) in guinea pig. Sinusoidal fluctuations appear to be an essential component of the pacemaking process. 相似文献
2.
Cardiac pacemaking in the sinoatrial (SA) node and atrioventricular (AV) node is generated by an interplay of many ionic currents, one of which is the funny pacemaker current ( If). To understand the functional role of If in two different pacemakers, comparative studies of spontaneous activity and expression of the HCN channel in mouse SA node and AV node were performed. The intrinsic cycle length (CL) is 179±2.7 ms ( n=5) in SA node and 258±18.7 ms ( n=5) in AV node. Blocking of If current by 1 μmol/L ZD7288 increased the CL to 258±18.7 ms ( n=5) and 447±92.4 ms ( n=5) in SA node and AV node, respectively. However, the major HCN channel, HCN4 expressed at low level in the AV node compared to the SA node. To clarify the discrepancy between the functional importance of If and expression level of HCN4 channel, a SA node cell model was used. Increasing the If conductance resulted in decreasing in the CL in the model, which explains the high pacemaking rate and high expression of HCN channel in the SA node. Resistance to the blocking of If in the SA node might result from compensating effects from other currents (especially voltage sensitive currents) involved in pacemaking. The computer simulation shows that the difference in the intrinsic CL could explain the difference in response to If blocking in these two cardiac nodes. 相似文献
3.
We have formulated a spatial-gradient model of action potential heterogeneity within the rabbit sinoatrial node (SAN), based on cell-specific ionic models of electrical activity from its central and peripheral regions. The ionic models are derived from a generic cell model, incorporating five background and exchange currents, and seven time-dependent currents based on three- or four-state Markov schemes. State transition rates are given by non-linear sigmoid functions of membrane potential. By appropriate selection of parameters, the generic model is able to accurately reproduce a wide range of action potential waveforms observed experimentally. Specifically, the model can fit recordings from central and peripheral regions of the SAN with RMS errors of 0.3987 and 0.7628 mV, respectively. Using a custom least squares parameter optimisation routine, we have constructed a spatially-varying gradient model that exhibits a smooth transition in action potential characteristics from the central to the peripheral region, whilst ensuring individual membrane currents remain physiologically accurate. Smooth transition action potential characteristics include maximum diastolic potential, overshoot potential, upstroke velocity, action potential duration and cycle length. The gradient model is suitable for developing higher dimensional models of the right atrium, in which action potential heterogeneity within nodal tissue may be readily incorporated. 相似文献
4.
The dynamics of establishing a unified sinoatrial node rhythm are considered. Mutual synchronization is shown to result in phase shifts and excitation delays. Rhythmogenesis in systems of two or many interacting pacemaker cells is examined in several point models and distributed models (Noble, Bonhoeffer-van der Pol, FitzHugh, Hodgkin-Huxley, Morris-Lecar). 相似文献
5.
The analysis of bifurcating solutions in the Totafurno and Trainor [23] model of supernumerary limb production in salamanders is re-examined using the symmetry analysis developed by Totafurno [22]. In particular, we show analytically that the appearance of field solutions possessing 2 and 4 singularities (the 2- and 4-centered solutions, respectively) also correspond to true bifurcations with reduced symmetries, just as had been previously found for a solution to the field equations not possessing such singularities (the twist solution). While the results have significance primarily for the biological problem, this work serves as an instructive example of the application of symmetry groups to the bifurcation analysis of nonlinear field equations arising from a variational principle. The relationship between the solutions of the nonlinear equations and the corresponding linear equations is discussed.Supported by the National Sciences and Engineering Research Council and the Medical Research Council of CanadaTo whom correspondence should be sent 相似文献
6.
Most classical prey-predator models do not take into account the behavioural structure of the population. Usually, the predator and the prey populations are assumed to be homogeneous, i.e. all individuals behave in the same way. In this work, we shall take into account different tactics that predators can use for exploiting a common self-reproducing resource, the prey population. Predators fight together in order to keep or to have access to captured prey individuals. Individual predators can use two behavioural tactics when they encounter to dispute a prey, the classical hawk and dove tactics. We assume two different time scales. The fast time scale corresponds to the inter-specific searching and handling for the prey by the predators and the intra-specific fighting between the predators. The slow time scale corresponds to the (logistic) growth of the prey population and mortality of the predator. We take advantage of the two time scales to reduce the dimension of the model and to obtain an aggregated model that describes the dynamics of the total predator and prey densities at the slow time scale. We present the bifurcation analysis of the model and the effects of the different predator tactics on persistence and stability of the prey-predator community are discussed. 相似文献
7.
Mechanical contraction of a cardiac muscle cell is related to the electric activation of the plasma membrane. As in the neuron cell, inflow of the Na(+) ions across the cell membrane causes electric activation with amplitude of about 100 mV. However, differently from the nerve cell, the action potential lasts a few hundred milliseconds before repolarization. Moreover, several types of K(+) channel such as the classical inward rectifier K(+) channel, the voltage dependent channel and others are responsible for the formation of the action potential. The mechanism of opening and closing the K(+) channels is not thoroughly elucidated. In the present paper, a four state Markov model with one open and three closed states is studied to obtain open and close probabilities of the gates constituting a specific ionic channel. The probability density functions of durations of opening and closing of the channel are also discussed. 相似文献
8.
In vivo biotelemetry studies have demonstrated that heart rate (HR) is progressively and rapidly reduced after administration
of streptozotocin (STZ) and that the reduction in HR can be partially normalized with insulin replacement. Reductions in HR
have also been reported in isolated perfused heart and superfused right atrial preparations suggesting that intrinsic defects
in the heart are at least partly responsible for the bradycardia. The regional effects of STZ-induced diabetes mellitus (DM)
on action potentials (APs) in the sinoatrial node (SAN), right and left atria and ventricles have been compared in the spontaneously
beating Langendorff perfused rat heart 10–12 weeks after treatment. HR was significantly reduced in STZ-induced diabetic rat
heart (174 ± 9 BPM) compared to controls (241 ± 12 BPM). The duration of AP repolarization at 50% and 70% from peak AP was
significantly prolonged in SAN, right atrium and right ventricle from STZ-induced diabetic rat compared to age-matched controls.
In the SAN AP duration (APD) at 50% and 70% were 51.7 ± 2.2 and 59.5 ± 2.3 ms in diabetic rat heart compared to 45.2 ± 1.7
and 50.0 ± 1.6 ms in controls, respectively. In contrast APD at 50% and 70% were not significantly altered in the left atrium
and left ventricle. Regional defects in the expression and/or electrophysiology of SAN ion channels, and in particular those
involved in AP repolarization, might underlie heart rhythm disturbances in the STZ-induced DM rat. 相似文献
9.
A kinetic model of plant nutrition described by Cloutier et al. (Cloutier et al., 2008. Biotechnol Bioeng 99:189-200) is progressively simplified so as to obtain a predictive model that describes the evolution of the biomass and the extracellular and intracellular concentrations of three determining nutrients, that is, free intracellular nitrogen, phosphate, and carbohydrate compounds. Three techniques of global sensitivity analysis are successively applied to assess the model parameter influence and potential correlation. The resulting dynamic model is able to predict plant growth for the two most encountered plant bioprocesses, namely suspension cells and hairy roots. 相似文献
10.
AIMS: To characterize the effects of inhibition of Ryanodine receptor (RyR), TTX-sensitive neuronal Na+ current (iNa), "rapidly activating" delayed rectifier K+ current (iKr) and ultrarapid delayed rectifier potassium current (IKur) on the pacemaker activity of the sinoatrial node (SAN) and the atrioventricular node (AVN) in the mouse. METHODS: The structure of mouse AVN was studied by histology and immunolabelling of Cx43 and hyperpolarization-activated, cyclic nucleotide-binding channels (HCN). The effects of Ryanodine, TTX, E-4031 and 4-AP on pacemaker activities recorded from mouse intact SAN and AVN preparations have been investigated. RESULTS: Immuno-histological characterization delineated the structure of the AVN showing the similar molecular phenotype of the SAN. The effects of these inhibitors on the cycle length (CL) of the spontaneous pacemaker activity of the SAN and the AVN were characterized. Inhibition of RyR by 0.2 and 2 microM Ryanodine prolonged CL by 42+/-12.3% and 64+/-18.1% in SAN preparations by 163+/-72.3% and 241+/-91.2% in AVN preparations. Inhibition of TTX-sensitive iNa by 100 nM TTX prolonged CL by 22+/-6.0% in SAN preparations and 53+/-13.6% in the AVN preparations. Block of iKr by E-4031 prolonged CL by 68+/-12.5% in SAN preparations and 28+/-3.4% in AVN preparations. Inhibition of iKur by 50 microM 4-AP prolonged CL by 20+/-3.4% in SAN preparations and 18+/-3.0% in AVN preparations. CONCLUSION: Mouse SAN and AVN showed distinct different response to the inhibition of RyR, TTX-sensitive INa, IKr and iKur, which reflects the variation in contribution of these currents to the pacemaker function of the cardiac nodes in the mouse. Our data provide valuable information for developing virtual tissue models of mouse SAN and AVN. 相似文献
11.
参数灵敏度分析旨在评价模型中各参数对模拟结果的影响程度,是参数优化和模型校正的基础步骤,也是认识模型行为的重要工具。所建的胶州湾生物-物理耦合模型包括浮游植物、浮游动物、营养盐、碎屑和溶解氧5类状态变量,对其涉及的50个参数进行灵敏度分析,得到3个非常灵敏性参数、2个灵敏性参数、11个比较灵敏性参数和34个不太灵敏性参数。非常灵敏及灵敏性参数包括浮游植物生长速率(μPRPC)、暗反应修正因子(FAC)、光饱和强度(α)、浮游植物死亡率(μDEPC)和水体消光系数(bla),主要影响浮游植物生长和死亡过程,反映了浮游植物在生态系统中的基础性和重要性作用。这5个参数显著地影响碳和营养盐循环,是整个胶州湾生态系统最主要的影响参数,应优先进行优化。比较灵敏性参数的影响主要表现在营养盐对浮游植物生长或死亡的限制以及温度对光饱和量的限制,浮游动物生长、牧食和死亡过程以及浮游植物生物量对牧食的限制,叶绿素a的生产,缺氧条件下沉积物释放磷以及浮游植物对磷的摄取等过程,这些参数对于各状态变量的灵敏性存在不同程度的差异,从而表征不同的特点。与不太灵敏性参数相关的过程主要为叶绿素a和碎屑消光作用,温度对浮游植物生长、浮游动物牧食、碎屑和沉积物矿化的限制,碎屑和沉积物矿化与沉降,与无机氮相关的大部分过程,溶解氧浓度变化等,这些过程除了受模型内部参数影响外,还在很大程度上受水深、海水温度和陆源污染等外部因素影响。比较灵敏及不太灵敏性参数影响模型局部过程,是模型校正的重要依据,除了非常灵敏及灵敏性参数以外,叶绿素a、浮游动物、碎屑和无机磷四种状态变量可分别根据叶绿素a最大生产系数(K CHmax)、浮游动物一级死亡率(μDEZC1)、有机碎屑矿化率(μREDC)和浮游植物磷摄取的半饱和常数(h UPPP)进行校正。与营养盐相关参数的灵敏度分析表明,胶州湾浮游植物处于磷限制,无机氮主要受陆源排污影响。因此,对无机氮的校正主要通过合理设置沿岸河流径流量或陆源污染物浓度与比例以及无机氮初始场。溶解氧对各参数均不太灵敏。 相似文献
12.
Many cellular functions are regulated by the Ca(2+) signal which contains specific information in the form of frequency, amplitude, and duration of the oscillatory dynamics. Any alterations or dysfunctions of components in the calcium signaling pathway of cardiac myocytes may lead to a diverse range of cardiac diseases including hypertrophy and heart failure. In this study, we have investigated the hidden dynamics of the intracellular Ca(2+) signaling and the functional roles of its regulatory mechanism through in silico simulations and parameter sensitivity analysis based on an experimentally verified mathematical model. It was revealed that the Ca(2+) dynamics of cardiac myocytes are determined by the balance among various system parameters. Moreover, it was found through the parameter sensitivity analysis that the self-oscillatory Ca(2+) dynamics are most sensitive to the Ca(2+) leakage rate of the sarcolemmal membrane and the maximum rate of NCX, suggesting that these two components have dominant effects on circulating the cytosolic Ca(2+). 相似文献
13.
Intracellular voltage transients of cultured cells are recorded by transistors and other planar electrodes as local extracellular
voltages. The theoretical relationship between extra- and intracellular voltage is investigated with a two-compartment circuit
using the approximation of a fast, weak and small cell-silicon junction. It is shown that extracellular recording relies on
the difference of specific ionic conductances in the attached and free regions of the cell membrane. The result rationalizes
various observations with neuron transistors. It guides the optimization of extracellular recording and the development of
cell-based chemical sensors.
Received: 13 August 1998 / Revised version: 9 October 1998 / Accepted: 9 October 1998 相似文献
15.
Lovelock于20世纪70年代提出了著名的盖娅假说,认为地球是一个由生物和非生物环境组成的“超级有机体”,有能力调节自身的气候和化学组成,使之适合于生物的生存.盖娅假说遭到了生物学家,尤其是新达尔文主义者的强烈批评,认为它是目的论;随后,Lovelock通过雏菊世界模型论证了该假说.模型中的黑雏菊和白雏菊通过反射较少或较多的太阳光来调节地球的温度.基于雏菊世界模型,通过假设不同的初始条件——不同初始面积分配和不同的太阳光反射率组合,运用系统动力学对雏菊世界的温度调节能力进行了敏感性分析.结果证明,既使初始条件有差异,雏菊世界仍能够通过自我调节机制调节系统稳定时的星球温度,达到最适合生物生存的温度.雏菊世界模型对于初始面积分配、光照反射率组合条件不敏感.最后,雏菊世界模型的优点在于系统分析思想和以及对地球系统的简化,但是随着人类活动对地球系统影响的日益显著,建议模型应包含更多的环境、生物变量以及反馈关系和人类活动因素,将盖娅系统融入到自然-人类耦合的大系统中. 相似文献
16.
Musculoskeletal models are used in order to describe and analyse the mechanics of human movement. In order to get a complete evaluation of the human movement, energetic muscle models were developed and were shown to be promising. The aim of this work is to determine the sensitivity of muscle mechanical and energetic model estimates to changes in parameters during recumbent pedalling. Inputs of the model were electromyography and joint angles, collected experimentally on one participant. The sensitivity analysis was performed on muscle-specific tension, physiological cross-sectional area, muscle maximal force, tendon rest length and percentage of fast-twitch fibres using an integrated sensitivity ratio. Soleus, gastrocnemius, vasti, gluteus and medial hamstrings were selected for the analyses. The energetic model was found to be always less sensitive to parameter changes than the mechanical model. Tendon slack length was found to be the most critical parameter for both energetic and mechanical models even if the effect on the energetic output was smaller than on muscle force and joint moments. 相似文献
17.
In farm animals, salivary cortisol has become a widely used parameter for measuring stress responses. However, only few studies have dealt with basal levels of concentration of cortisol in pigs and its circadian rhythm. The aim of this study was to examine the effects of ambient temperature and thermoregulatory behaviour on the circadian rhythm of salivary cortisol levels in fattening pigs. Subjects were 30 fattening pigs of different weight (60 to 100 kg), kept in six groups in an uninsulated building in pens with partly slatted floors. Saliva samples were taken every 2 h over periods of 24 h at different ambient temperatures at two times in winter and four times in summer. Thermoregulatory behaviour was recorded in the same 24-h time periods. The effect of time of day, body weight, ambient temperature and behaviour on the cortisol level was analysed using a mixed-effects model. Two peaks of cortisol levels per day were found. This circadian pattern became more pronounced with increasing weight and on days where thermoregulatory behaviour was shown. Mean cortisol levels per day were affected by weight but not by thermoregulatory behaviour. From our data, we conclude that long-term variations in cortisol concentration may be influenced by increasing age and weight more than by the respective experimental situation. In assessing animal welfare, it seems more reliable to consider the circadian pattern of cortisol concentration instead of only one value per day. 相似文献
18.
In this work we present a mathematical model describing the dynamics of a population where sex allocation remains flexible throughout adult life and so can be adjusted to current environmental conditions. We consider that the fractions of immature individuals acquiring male and female sexual roles are density dependent through nonlinear functions of a weighted total population size. The main goal of this work is to understand the role of life-history parameters on the stabilization or destabilization of the population dynamics.The model turns out to be a nonlinear discrete model which is analysed by studying the existence of fixed points as well as their stability conditions in terms of model parameters. The existence of more complex asymptotic behaviours of system solutions is shown by means of numerical simulations.Females have larger fertility rate than males. On the other hand, increasing population density favours immature individuals adopting the male role. A positive equilibrium of the system exists whenever fertility and survival rates of one of the sexual roles, if shared by all adults, allow population growing while the opposite happens with the other sexual role. In terms of the female inherent net reproductive number, ηF, it is shown that the positive equilibria are stable when ηF is larger and closed to 1 while for larger values of ηF a certain asymptotic assumption on the investment rate in the female function implies that the population density is permanent. Depending on the other parameters values, the asymptotic behaviour of solutions becomes more complex, even chaotic. In this setting the stabilization/destabilization effects of the abruptness rate in density dependence, of the survival rates and of the competition coefficients are analysed. 相似文献
19.
生态过程模型的发展为研究者在长时间序列和区域尺度的研究提供了便利, 但模型模拟的准确性受到模型自身结构、模型参数估计合理性的影响。敏感性分析能够定量或定性筛选出对模型模拟结果影响较大的敏感参数, 是模型参数校准过程中的重要工具, 也是建模和应用的先决条件。该文以阔叶红松林为研究对象, 采用全局敏感性分析方法——傅里叶幅度灵敏度检验扩展法(EFAST)对Biome-BGC模型的生理生态参数进行了敏感性分析, 分别分析了红松( Pinus koraiensis)和阔叶树的净初级生产力( NPP)、蒸散( ET)对参数变化的敏感性。结果表明: (1)模拟红松 NPP的不确定性高于阔叶树, 但二者的模拟 ET的不确定性均较小。阔叶树的 NPP和 ET对生理生态参数的敏感性总体上都小于红松。(2)无论是红松、阔叶或其他植被类型, 模拟 NPP均表现出对叶片碳氮比、细根碳氮比、比叶面积( SLA)和冠层截留系数的敏感性, 这4个参数的高敏感性主要是由模型自身结构所决定的, 与植被类型和研究地区的关系较小。对模拟 ET而言, 细根与叶片碳分配比、新茎与新叶碳分配比和 SLA均是影响红松和阔叶树 ET的敏感参数, 但红松 ET主要受参数与参数间的二阶或多阶交互作用的间接影响, 而阔叶树 ET则主要是受到敏感参数直接效应的影响。(3)除了上述影响红松和阔叶树碳水通量的共性参数外, 诸如核酮糖-1,5-二磷酸羧化酶中叶氮含量、叶片与细根周转率、所有叶面积与投影叶面积之比等也是对模拟结果有影响的重要参数, 但是其敏感程度随物种不同和研究区不同而不同, 所以这类参数可以根据具体情况进行参数本地化, 对于其他不敏感参数则可以采用模型缺省值。 相似文献
20.
Synchronization has been observed in various systems, including living beings. In a previous study, we reported a new phenomenon with antisynchronization in calling behavior of two interacting Japanese tree frogs. In this paper, we theoretically analyse nonlinear dynamics in a system of three coupled oscillators, which models three interacting frogs, where the oscillators of each pair have the property of antisynchronization; in particular, we perform bifurcation analysis and Lyapunov function analysis. 相似文献
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