How noise and coupling induce bursting action potentials in pancreatic {beta}-cells

Unlike isolated beta-cells, which usually produce continuous spikes or fast and irregular bursts, electrically coupled beta-cells are apt to exhibit robust bursting action potentials. We consider the noise induced by thermal fluctuations as well as that by channel-gating stochasticity and examine its effects on the action potential behavior of the beta-cell model. It is observed numerically that such noise in general helps single cells to produce a variety of electrical activities. In addition, we also probe coupling via gap junctions between neighboring cells, with heterogeneity induced by noise, to find that it enhances regular bursts.     

Afferent bursting activity of ruff lateral line induced by background noise stimulation

Summary Single unit resting activities were recorded from fibres innervating a neuromast of the supra-orbital canal of the lateral line system of the ruff (Acerina cernua). The interval histogram of 1 of the 4 types of resting activity had a bimodal distribution (bursting activity). The resting activity of these fibres was compared with the measured vibration of the experimental table. The conclusion that the bursting activity is not spontaneous but is caused by small background vibrations of the table was supported by recording of extracellular hair cell responses.Abbreviation ISI Interspike interval     

Channel sharing in pancreatic beta -cells revisited: enhancement of emergent bursting by noise

Secretion of insulin by electrically coupled populations of pancreatic beta -cells is governed by bursting electrical activity. Isolated beta -cells, however, exhibit atypical bursting or continuous spike activity. We study bursting as an emergent property of the population, focussing on interactions among the subclass of spiking cells. These are modelled by equipping the fast subsystem with a saddle-node-loop bifurcation, which makes it monostable. Such cells can only spike tonically or remain silent when isolated, but can be induced to burst with weak diffusive coupling. With stronger coupling, the cells revert to tonic spiking. We demonstrate that the addition of noise dramatically increases, via a phenomenon like stochastic resonance, the coupling range over which bursting is seen.     

Chaotic and irregular bursting electrical activity in mouse pancreatic B-cells.

The glucose-induced B-cell electrical activity was recorded in islets of Langerhans isolated from Swiss Webster albino mice originating from different suppliers. 23 out of 25 islets obtained from mice bred at the Charles River Breeding Station (CR mice) exhibited irregular or chaotic burst patterns of electrical activity, while 36 out of 40 islets isolated from mice bred locally at the National Institutes of Health displayed the typical bursting activity. The CR mice tended to recover a regular pattern after 1 mo on the National Institutes of Health mouse diet. The irregular or chaotic bursting electrical activity is proposed to result from changes in B-cell membrane composition or cellular metabolism, possibly induced by differences in diet.     

The electrical noise of a cell: correlations between resistance noise and voltage noise

A theory is developed for explaining the very low-frequency stochastic fluctuations of both the membrane voltage and the membrane conductance of a cell. It is shown that these fluctuations need not be correlated. However, in cells where the dominant transport mechanism is a potassium conductance, the theory predicts a significant negative correlation between the two with the relative fluctuations of the membrane conductance being much larger than those of the membrane voltage; this is in accord with previously published measurements.     

Dynamics of spiking neurons connected by both inhibitory and electrical coupling

We study the dynamics of a pair of intrinsically oscillating leaky integrate-and-fire neurons (identical and noise-free) connected by combinations of electrical and inhibitory coupling. We use the theory of weakly coupled oscillators to examine how synchronization patterns are influenced by cellular properties (intrinsic frequency and the strength of spikes) and coupling parameters (speed of synapses and coupling strengths). We find that, when inhibitory synapses are fast and the electrotonic effect of the suprathreshold portion of the spike is large, increasing the strength of weak electrical coupling promotes synchrony. Conversely, when inhibitory synapses are slow and the electrotonic effect of the suprathreshold portion of the spike is small, increasing the strength of weak electrical coupling promotes antisynchrony (see Fig. 10). Furthermore, our results indicate that, given a fixed total coupling strength, either electrical coupling alone or inhibition alone is better at enhancing neural synchrony than a combination of electrical and inhibitory coupling. We also show that these results extend to moderate coupling strengths.     

Hopf bifurcation and bursting synchronization in an excitable systems with chemical delayed coupling

In this paper we consider the Hopf bifurcation and synchronization in the two coupled Hindmarsh–Rose excitable systems with chemical coupling and time-delay. We surveyed the conditions for Hopf bifurcations by means of dynamical bifurcation analysis and numerical simulation. The results show that the coupled excitable systems with no delay have supercritical Hopf bifurcation, while the delayed system undergoes Hopf bifurcations at critical time delays when coupling strength lies in a particular region. We also investigated the effect of the delay on the transition of bursting synchronization in the coupled system. The results are helpful for us to better understand the dynamical properties of excitable systems and the biological mechanism of information encoding and cognitive activity.     

Neurotransmission: Chemical and electrical interneuron coupling

Recent studies have described the coupling between pairs of neocortical interneurons involving both electrical and chemical transmission; these new results may have important implications for the mechanisms underlying neuronal synchrony and rhythmic activity in the brain.     

Event-driven simulation of neural population synchronization facilitated by electrical coupling

Most neural communication and processing tasks are driven by spikes. This has enabled the application of the event-driven simulation schemes. However the simulation of spiking neural networks based on complex models that cannot be simplified to analytical expressions (requiring numerical calculation) is very time consuming. Here we describe briefly an event-driven simulation scheme that uses pre-calculated table-based neuron characterizations to avoid numerical calculations during a network simulation, allowing the simulation of large-scale neural systems. More concretely we explain how electrical coupling can be simulated efficiently within this computation scheme, reproducing synchronization processes observed in detailed simulations of neural populations.     

Role of single-channel stochastic noise on bursting clusters of pancreatic beta-cells.

To study why pancreatic beta-cells prefer to burst as a multi-cellular complex, we have formulated a stochastic model for bursting clusters of excitable cells. Our model incorporated a delayed rectifier K+ channel, a fast voltage-gated Ca2+ channel, and a slow Cai-blockable Ca2+ channel. The fraction of ATP-sensitive K+ channels that may still be active in the bursting regime was included in the model as a leak current. We then developed an efficient method for simulating an ionic current component of an excitable cell that contains several thousands of channels opening simultaneously under unclamped voltage. Single channel open-close stochastic events were incorporated into the model by use of binomially distributed random numbers. Our simulations revealed that in an isolated beta-cell [Ca2+]i oscillates with a small amplitude about a low [Ca2+]i. However, in a large cluster of tightly coupled cells, stable bursts develop, and [Ca2+]i oscillates with a larger amplitude about a higher [Ca2+]i. This may explain why single beta-cells do not burst and also do not release insulin.     

Beat-to-beat repolarization variability in ventricular myocytes and its suppression by electrical coupling

Single ventricular myocytes paced at a constant rate and held at a constant temperature exhibit beat-to-beat variations in action potential duration (APD). In this study we sought to quantify this variability, assess its mechanism, and determine its responsiveness to electrotonic interactions with another myocyte. Interbeat APD(90) (90% repolarization) of single cells was normally distributed. We thus quantified APD(90) variability as the coefficient of variability, CV = (SD/mean APD(90)) x 100. The mean +/- SD of the CV in normal solution was 2.3 +/- 0.9 (132 cells). Extracellular TTX (13 microM) and intracellular EGTA (14 mM) both significantly reduced the CV by 44 and 26%, respectively. When applied in combination the CV fell by 54%. In contrast, inhibition of the rapid delayed rectifier current with L-691,121 (100 nM) increased the CV by 300%. The CV was also significantly reduced by 35% when two normal myocytes were electrically connected with a junctional resistance (R(j)) of 100 MOmega. Electrical coupling (R(j) = 100 MOmega) of a normal myocyte to one producing early afterdepolarization (EAD) completely blocked EAD formation. These results indicate that beat-to-beat APD variability is likely mediated by stochastic behavior of ion channels and that electrotonic interactions act to limit temporal dispersion of refractoriness, a major contributor to arrhythmogenesis.     

Long-distance electrical coupling via tunneling nanotubes

Tunneling nanotubes (TNTs) are nanoscaled, F-actin containing membrane tubes that connect cells over several cell diameters. They facilitate the intercellular exchange of diverse components ranging from small molecules to organelles and pathogens. In conjunction with recent findings that TNT-like structures exist in tissue, they are expected to have important implications in cell-to-cell communication. In this review we will focus on a new function of TNTs, namely the transfer of electrical signals between remote cells. This electrical coupling is not only determined by the biophysical properties of the TNT, but depends on the presence of connexons interposed at the membrane interface between TNT and the connected cell. Specific features of this coupling are compared to conventional gap junction communication. Finally, we will discuss possible down-stream signaling pathways of this electrical coupling in the recipient cells and their putative effects on different physiological activities. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.     

基因转录爆发的信号转导机制

随着单分子检测技术水平的提高,学术界发现了与传统认知大相径庭的转录现象——转录爆发。基因转录不是连续平稳且波动较小的过程,而是表现出发生时间极不规律、信使RNA产量波动极大的特征。转录爆发本质上是编码和传递调控信号的方式。本文综述了转录爆发现象、转录爆发的两态模型、转录爆发信号转导机制以及其重要的生物学意义。最后,指出了该领域亟待解决的问题。     

Phantom bursting is highly sensitive to noise and unlikely to account for slow bursting in beta-cells: considerations in favor of metabolically driven oscillations

Pancreatic beta-cells show bursting electrical activity with a wide range of burst periods ranging from a few seconds, often seen in isolated cells, over tens of seconds (medium bursting), usually observed in intact islets, to several minutes. The phantom burster model [Bertram, R., Previte, J., Sherman, A., Kinard, T.A., Satin, L.S., 2000. The phantom burster model for pancreatic beta-cells. Biophys. J. 79, 2880-2892] provided a framework, which covered this span, and gave an explanation of how to obtain medium bursting combining two processes operating on different time scales. However, single cells are subjected to stochastic fluctuations in plasma membrane currents, which are likely to disturb the bursting mechanism and transform medium bursters into spikers or very fast bursters. We present a polynomial, minimal, phantom burster model and show that noise modifies the plateau fraction and lowers the burst period dramatically in phantom bursters. It is therefore unlikely that slow bursting in single cells is driven by the slow phantom bursting mechanism, but could instead be driven by oscillations in glycolysis, which we show are stable to random ion channel fluctuations. Moreover, so-called compound bursting can be converted to apparent slow bursting by noise, which could explain why compound bursting and mixed Ca(2+) oscillations are seen mainly in intact islets.     

Variability of bursting patterns in a neuron model in the presence of noise

Spiking and bursting patterns of neurons are characterized by a high degree of variability. A single neuron can demonstrate endogenously various bursting patterns, changing in response to external disturbances due to synapses, or to intrinsic factors such as channel noise. We argue that in a model of the leech heart interneuron existing variations of bursting patterns are significantly enhanced by a small noise. In the absence of noise this model shows periodic bursting with fixed numbers of interspikes for most parameter values. As the parameter of activation kinetics of a slow potassium current is shifted to more hyperpolarized values of the membrane potential, the model undergoes a sequence of incremental spike adding transitions accumulating towards a periodic tonic spiking activity. Within a narrow parameter window around every spike adding transition, spike alteration of bursting is deterministically chaotic due to homoclinic bifurcations of a saddle periodic orbit. We have found that near these transitions the interneuron model becomes extremely sensitive to small random perturbations that cause a wide expansion and overlapping of the chaotic windows. The chaotic behavior is characterized by positive values of the largest Lyapunov exponent, and of the Shannon entropy of probability distribution of spike numbers per burst. The windows of chaotic dynamics resemble the Arnold tongues being plotted in the parameter plane, where the noise intensity serves as a second control parameter. We determine the critical noise intensities above which the interneuron model generates only irregular bursting within the overlapped windows.     

Effect of cadmium ions on bursting electrical activity of an identified snail neuron

The effect of cadmium ions, a specific blocker of the inward calcium current in molluscan neurons, on electrical activity of identified neuron RPal ofHelix pomatia was studied. Cadmium ions in a concentration of 1 mM were shown to block bursting activity of the neuron completely. The membrane potential increased under these circumstances to about ?65 mV. After rinsing out the cadmium ions electrical activity in the neuron was fully restored. If a modulating factor (a peptide fraction obtained from the water-soluble part of snail brain homogenate) was added to the solution containing cadmium ions, however, not only was bursting activity not blocked, but it was actually intensified. Addition of modulating factor to the solution after blocking induced by cadmium ions led to the reappearance of bursting activity if not more than a few tens of seconds had elapsed after blocking developed. As the time after the beginning of blocking increased, addition of the modulating factor became less effective and caused only rhythmic activity to develop. It was concluded from the results of these experiments that bursting activity of neuron RPal is not endogenous but is induced in it by a modulating factor secreted by an unidentified peptidergic interneuron. Calcium ions do not play an essential role in the generation of slow depolarization waves in the neuron under these circumstances but they are essential for secretion of the modulating factor.     

Regulation of intermuscular electrical coupling by the Caenorhabditis elegans innexin inx-6

The innexins represent a highly conserved protein family, the members of which make up the structural components of gap junctions in invertebrates. We have isolated and characterized a Caenorhabditis elegans gene inx-6 that encodes a new member of the innexin family required for the electrical coupling of pharyngeal muscles. inx-6(rr5) mutants complete embryogenesis without detectable abnormalities at restrictive temperature but fail to initiate postembryonic development after hatching. inx-6 is expressed in the pharynx at all larval stages, and an INX-6::GFP fusion protein showed a punctate expression pattern characteristic of gap junction proteins localized to plasma membrane plaques. Video recording and electropharyngeograms revealed that in inx-6(rr5) mutants the anterior pharyngeal (procorpus) muscles were electrically coupled to a lesser degree than the posterior metacorpus muscles, which caused a premature relaxation in the anterior pharynx and interfered with feeding. Dye-coupling experiments indicate that the gap junctions that link the procorpus to the metacorpus are functionally compromised in inx-6(rr5) mutants. We also show that another C. elegans innexin, EAT-5, can partially substitute for INX-6 function in vivo, underscoring their likely analogous function.