Slow Bursts Research Articles

Different bifurcations and slow dynamics underlying different stochastic dynamics of slow, medium, and fast bursting of β-cell

Different bifurcations and slow dynamics underlying different stochastic dynamics of slow, medium, and fast bursting of β-cell

Distributed fiber optic strain sensing for structural health monitoring of 70 MPa hydrogen vessels

We report on the development and testing of 70 MPa hydrogen pressure vessels with integrated fiber optic sensing fibers for the automotive use. The paper deals with the condition monitoring of such composite pressure vessels using the optical backscatter reflectometry (OBR) which was applied for a distributed fiber optic strain sensing along fully integrated polyimide-coated single-mode glass optical fiber (SM-GOF). The sensing fibers were embedded into the vessel structure by wrapping them over the inside polymer liner during the manufacturing process of the outside carbon fiber reinforced polymer (CFRP). Detecting local strain events by the integrated fiber optic sensors might be an opportunity for monitoring the material degradation. Regarding the investigation of the ageing behavior, both ambient hydraulic cycling tests and slow burst tests were conducted on 70 MPa pressure vessels with embedded fiber optic sensors. The achieved results contribute to the knowledge about material fatigue to guarantee the safe usage during the entire lifetime of the composite hydrogen storage vessels. The presented work stands in context of the European Horizon 2020 research project SH2APED focused on the development of an innovative hydrogen storage system composed of an assembly of nine 70 MPa tubular pressure vessels used as an automotive battery pack.

Switching neuron contributions to second network activity.

Network flexibility is important for adaptable behaviors. This includes neuronal switching, where neurons alter their network participation, including changing from single- to dual-network activity. Understanding the implications of neuronal switching requires determining how a switching neuron interacts with each of its networks. Here, we tested 1) whether "home" and second networks, operating via divergent rhythm generation mechanisms, regulate a switching neuron and 2) if a switching neuron, recruited via modulation of intrinsic properties, contributes to rhythm or pattern generation in a new network. Small, well-characterized feeding-related networks (pyloric, ∼1 Hz; gastric mill, ∼0.1 Hz) and identified modulatory inputs make the isolated crab (Cancer borealis) stomatogastric nervous system (STNS) a useful model to study neuronal switching. In particular, the neuropeptide Gly1-SIFamide switches the lateral posterior gastric (LPG) neuron (2 copies) from pyloric-only to dual-frequency pyloric/gastric mill (fast/slow) activity via modulation of LPG-intrinsic properties. Using current injections to manipulate neuronal activity, we found that gastric mill, but not pyloric, network neurons regulated the intrinsically generated LPG slow bursting. Conversely, selective elimination of LPG from both networks using photoinactivation revealed that LPG regulated gastric mill neuron-firing frequencies but was not necessary for gastric mill rhythm generation or coordination. However, LPG alone was sufficient to produce a distinct pattern of network coordination. Thus, modulated intrinsic properties underlying dual-network participation may constrain which networks can regulate switching neuron activity. Furthermore, recruitment via intrinsic properties may occur in modulatory states where it is important for the switching neuron to actively contribute to network output.NEW & NOTEWORTHY We used small, well-characterized networks to investigate interactions between rhythmic networks and neurons that switch their network participation. For a neuron switching into dual-network activity, only the second network regulated its activity in that network. In addition, the switching neuron was sufficient but not necessary to coordinate second network neurons and regulated their activity levels. Thus, regulation of switching neurons may be selective, and a switching neuron is not necessarily simply a follower in additional networks.

The aggregation of casein micelles induced by Ca2+ during in vitro digestion: effects on the release of loaded anthocyanins.

Colloidal calcium phosphate (CCP) confers a modifiable structure to micellar casein (MC), which endows it with potential advantages as a delivery carrier. However, it is difficult to achieve multipattern release of the core material in the intestine with MC as a single wall. In this study, we prepared an anthocyanin-casein-based delivery system utilizing MC with different freezing degrees as the wall material with the objective of achieving the controlled release of anthocyanin as the model core in the intestine. The results showed that freezing could significantly reduce the CCP level up to 50%. Static in vitro simulated digestion with the addition of exogenous Ca2+ showed that the designed delivery system exhibited low anthocyanin release (15%-35%) in the gastric tract. The pattern of release in the intestine depended on the CCP dissociation degree. High and low dissociation degrees corresponded to slow release (from 15% to 65% within 2 h) and burst release (from 35% to 90% within 5 min), respectively. WAXS/SAXS analysis revealed that exogenous serum Ca2+ inherent in simulated gastric fluid and endogenous serum Ca2+ induced by CCP dissociation was synergistically involved in the reconstitution of CCP-mediated nanoclusters and large aggregates. The freezing degree of MC determined the endogenous serum Ca2+ level, which influenced the gastric aggregation behavior of wall MC and ultimately led to a fairly different gastrointestinal release behavior of anthocyanins.

Intratumoral thermo-chemotherapeutic alginate hydrogel containing doxorubicin loaded PLGA nanoparticle and heating agent

Chemotherapy has been widely used to treat cancer; however, the non-specific systemic toxicity of chemotherapeutic agents has always been an issue. Local injection treatment is a strategy used to reduce the undesired adverse effects of chemotherapeutic drugs. In addition, chemotherapeutic agents combined with thermotherapy are effective in further enhancing therapeutic potency. In the present study, we prepared an injectable hydrogel, namely, doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticle (DPN) and magnetite nanoparticle (MNP) embedded in alginate hydrogel (DPN/MNP-HG), where DPN and MNP were the chemotherapeutic and heating agents, respectively, for intratumoral thermo-chemotherapy. Injectable DPN/MNP-HG, which possesses solid-like elastic properties, was conveniently prepared via ionic cross-linking at room-temperature. When exposed to an alternating magnetic field (AMF), DPN/MNP-HG exhibited controllable heat generation with a reversible temperature-rise profile. Regarding the kinetics of DOX release, both with and without AMF, DPN/MNP-HG exhibited a slow initial burst and sustained release profile. In cytotoxicity studies and subcutaneous mouse cancer models, successful thermo-chemotherapy with DPN/MNP-HG resulted in significantly lower cell viability and increased tumor-growth suppression; mice also exhibited good tolerance to injected DPN/MNP-HG both with(+) and without AMF application. In conclusion, the proposed thermo-chemotherapeutic DPN/MNP-HG for local intratumoral injection is a promising formulation for cancer treatment.

Dopamine D1-receptor-expressing pathway from the nucleus accumbens to ventral pallidum-mediated sevoflurane anesthesia in mice.

General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep-wake system may play a role in the reversible loss of consciousness induced by general anesthetics. Studies in mice have shown that microinjection of dopamine receptor 1 (D1R) agonists into the nucleus accumbens (NAc) promotes recovery from isoflurane anesthesia, while microinjection of D1R antagonists has the opposite effect. Furthermore, during the induction and maintenance of sevoflurane anesthesia, there is a significant decrease in extracellular dopamine levels in the NAc, which subsequently increases during the recovery period. These findings suggest the involvement of the NAc in the regulation of general anesthesia. However, the specific role of D1R-expressing neurons in the NAc during general anesthesia and the downstream effect pathways are still not well understood. In order to analyze the impact of sevoflurane anesthesia on NAcD1R neurons and the NAcD1R -VP pathway, this study employed calcium fiber photometry to investigate alterations in the fluorescence intensity of calcium signals in dopamine D1-receptor-expressing neurons located in the nucleus accumbens (NAcD1R neurons) and the NAcD1R -VP pathway during sevoflurane anesthesia. Subsequently, optogenetic techniques were utilized to activate or inhibit NAcD1R neurons and their synaptic terminals in the ventral pallidum (VP), aiming to elucidate the role of NAcD1R neurons and the NAcD1R -VP pathway in sevoflurane anesthesia. These experiments were supplemented with electroencephalogram (EEG) recordings and behavioral tests. Lastly, a genetically-encoded fluorescent sensor was employed to observe changes in extracellular GABA neurotransmitters in the VP during sevoflurane anesthesia. Our findings revealed that sevoflurane administration led to the inhibition of NAcD1R neuron population activity, as well as their connections within the ventral pallidum (VP). We also observed a reversible reduction in extracellular GABA levels in the VP during both the induction and emergence phases of sevoflurane anesthesia. Additionally, the optogenetic activation of NAcD1R neurons and their synaptic terminals in the VP resulted in a promotion of wakefulness during sevoflurane anesthesia, accompanied by a decrease in EEG slow wave activity and burst suppression rate. Conversely, the optogenetic inhibition of the NAcD1R -VP pathway exerted opposite effects. The NAcD1R -VP pathway serves as a crucial downstream pathway of NAcD1R neurons, playing a significant role in regulating arousal during sevoflurane anesthesia. Importantly, this pathway appears to be associated with the release of GABA neurotransmitters from VP cells.

Passive limb training modulates respiratory rhythmic bursts

Exercise modifies respiratory functions mainly through the afferent feedback provided by exercising limbs and the descending input from suprapontine areas, two contributions that are still underestimated in vitro. To better characterize the role of limb afferents in modulating respiration during physical activity, we designed a novel experimental in vitro platform. The whole central nervous system was isolated from neonatal rodents and kept with hindlimbs attached to an ad-hoc robot (Bipedal Induced Kinetic Exercise, BIKE) driving passive pedaling at calibrated speeds. This setting allowed extracellular recordings of a stable spontaneous respiratory rhythm for more than 4 h, from all cervical ventral roots. BIKE reversibly reduced the duration of single respiratory bursts even at lower pedaling speeds (2 Hz), though only an intense exercise (3.5 Hz) modulated the frequency of breathing. Moreover, brief sessions (5 min) of BIKE at 3.5 Hz augmented the respiratory rate of preparations with slow bursting in control (slower breathers) but did not change the speed of faster breathers. When spontaneous breathing was accelerated by high concentrations of potassium, BIKE reduced bursting frequency. Regardless of the baseline respiratory rhythm, BIKE at 3.5 Hz always decreased duration of single bursts. Surgical ablation of suprapontine structures completely prevented modulation of breathing after intense training. Albeit the variability in baseline breathing rates, intense passive cyclic movement tuned fictive respiration toward a common frequency range and shortened all respiratory events through the involvement of suprapontine areas. These observations contribute to better define how the respiratory system integrates sensory input from moving limbs during development, opening new rehabilitation perspectives.

FRB–SRB–XRB: Geometric and relativistic beaming constraints of fast radio bursts from the Galactic magnetar SGR J1935+2154

ABSTRACT The detection of a fast radio burst (FRB), FRB 200428, coincident with an X-ray burst (XRB) from the Galactic magnetar soft gamma repeater (SGR) SGR J1935+2154 suggests that magnetars can produce FRBs. Many XRBs have been detected from the source, but very few were found to be associated with bursty radio emission. Meanwhile, a number of weaker radio bursts have been detected from the source, which could in principle be slow radio bursts (SRBs): FRBs detected at viewing angles outside the FRB jet cone. In this paper, we use these X-ray and radio observations to constrain the geometric and relativistic beaming factors of FRBs under two hypotheses. First, we assume that all SRBs should be associated with XRBs like FRB 200428. We use the FRB–SRB closure relations to identify two SRBs and derive that FRB beaming must be geometrically narrow, θj ≲ 10−2 rad and follow θjΓ ∼ 2. Second, we assume a less stringent constraint for SRBs by not requiring that they are associated with XRBs. We identify a total of seven SRBs, five of which have Gaussian-like spectra, and derive that FRB beaming factors again follow θjΓ ∼ 2.

Preparation of PLGA-Coated Porous Silica Nanofibers for Drug Release.

Fibrous materials have unique applications in drug release and biomedical fields. This study reports on the preparation of porous silica nanofibers, using organic nanofibers as templates, and their use for drug release. Different from the commonly used electrospinning method, the organic nanofibers are produced via a self-assembly approach between melamine and benzene-1,3,5-tricarboxylic acid. Silica is then coated on the organic nanofibers via homogenization in a silica sol, a freeze-drying process, and then a sol-gel process. In order to regulate the surface area and mesopore volume of silica nanofibers, cetyltrimethyl ammonium bromide at different concentrations is used as template in the sol-gel process. With the removal of organic nanofibers and the surfactant by calcination, porous silica nanofibers are generated and then assessed as a scaffold for controlled drug release with ketoprofen as a model drug. Poly (D, L-lactide-co-glycolide) is coated on the silica nanofibers to achieve slow burst release and prolonged cumulative release of 25 days. This study demonstrates an effective method of preparing hollow silica nanofibers and the use of such nanofibers for long-term release with high drug loading.

Bursting oscillation of a pendulum with irrational nonlinearity

The bursting oscillation has attracted lots of attention due to its complex dynamical behaviors. However, most models are based on polynomial nonlinearity, and the irrational nonlinearity has not been considered by researchers. Particularly, it is a typical nonlinear model that has been widely utilized in engineering fields, so it is urgent to investigate the bursting behaviors of the system. To realize this task, this paper explores a novel bursting oscillation of a pendulum with irrational nonlinearity. Three typical cases of excitation patterns are employed to investigate the complicated bursting behaviors. The mechanism of slow bursting response and the stability of equilibrium points are analyzed via the multiple time scale dynamics method. The three-parameter, two-parameter, and one-parameter bifurcations are proposed. Four new types of bifurcations, namely, forked-, spindle-, saddle- and camelback-shaped bifurcations are observed. The bursting trajectory and jumping characteristics are examined by employing the transformed phase. Finally, the multi-valued phenomenon is performed via the basin of attraction.

The effects of slow breathing on postural muscles during standing perturbations in young adults.

Maintaining standing balance is vital to completing activities in daily living. Recent findings suggest an interaction between cardiovascular and postural control systems. Volitional slow breathing can modulate the cardiovascular response and affect postural control during quiet standing. However, the effects of slow breathing during threats to standing balance have not been studied. The study examined the effect of slow breathing on the latency and amplitude of postural muscle responses to perturbations of the base of support in healthy, young adults. Twenty-seven participants completed two balance perturbation tasks in standing on an instrumented split-belt treadmill while breathing spontaneously and breathing at 6 breaths per minute. Each perturbation task consisted of 25 posteriorly directed translations of the treadmill belts every 8-12s. Muscle latency and muscle burst amplitude were measured using surface electromyography from the right limb for the quadriceps (QUADS), medial hamstring (MH), gastrocnemii (GASTROC), soleus (SOL), and tibialis anterior (TA) muscle groups, while a respiratory belt was used to record respiratory rate. Results indicated that during the slow breathing task both muscle latency (p = 0.022) and muscle burst amplitude (p = 0.011) decreased compared to spontaneous breathing. The EMG pre-perturbation activation was not significantly different in any muscle group between conditions (p > 0.167). The study found that reducing respiratory rate to approximately 6 breaths per minute affects the neuromuscular responses in the lower limb muscles to perturbations.

The bioelectrical conduction system around the ileocecal junction defined through in vivo high-resolution mapping in rabbits.

Coordinated contractions across the small and large intestines via the ileocecal junction (ICJ) are critical to healthy gastrointestinal function and are in part governed by myoelectrical activity. In this study, the spatiotemporal characteristics of the bioelectrical conduction across the ICJ and its adjacent regions were quantified in anesthetized rabbits. High-resolution mapping was applied from the terminal ileum (TI) to the sacculus rotundus (SR), across the ICJ and into the beginning of the large intestine at the cecum ampulla coli (AC). Orally propagating slow wave patterns in the SR did not entrain the TI. However, aborally propagating patterns from the TI were able to entrain the SR. Bioelectrical activity was recorded within the ICJ and AC, revealing complex interactions of slow waves, spike bursts, and bioelectrical quiescence. This suggests the involvement of myogenic coordination when regulating motility between the small and large intestines. Mean slow wave frequency between regions did not vary significantly (13.74-17.16 cycles/min). Slow waves in the SR propagated with significantly faster speeds (18.51 ± 1.57 mm/s) compared with the TI (14.05 ± 2.53 mm/s, P = 0.0113) and AC (9.56 ± 1.56 mm/s, P = 0.0001). Significantly higher amplitudes were observed in both the TI (0.28 ± 0.13 mV, P = 0.0167) and SR (0.24 ± 0.08 mV, P = 0.0159) within the small intestine compared with the large intestine AC (0.03 ± 0.01 mV). We hypothesize that orally propagating slow waves facilitate a motor-brake pattern in the SR to limit outflow into the ICJ, similar to those previously observed in other gastrointestinal regions.NEW & NOTEWORTHY Competing slow wave pacemakers were observed in the terminal ileum and sacculus rotundus. Prevalent oral propagation in the sacculus rotundus toward the terminal ileum potentially acts as a brake mechanism limiting outflow. Slow waves and periods of quiescence at the ileocecal junction suggest that activation may depend on the coregulatory flow and distention pathways. Slow waves and spike bursts in the cecum impart a role in the coordination of motility.

Differences in External Morphology, Body Composition and Swimming Performance Between Hatchery- and Wild-Origin Marbled Rockfish (Sebastiscus marmoratus)

Stock enhancement based on hatchery-reared fish has become one of the most common forms of management practices in marine fisheries resource restoration. However, unnatural rearing environments may cause hatchery-reared fish to diverge phenotypically from wild conspecifics, with negative consequences for post-release performance in the natural environments. To better evaluate the suitability of releasing hatchery-reared fish, it is necessary to understand the phenotypic effects of captive rearing, through comparisons with wild conspecifics. In this study, we compared body morphology, swimming performance, and biochemical body composition between hatchery-reared and wild marbled rockfish (Sebastiscus marmoratus) from the same general gene pool. The results show that the overall body profile differed significantly between the groups, with hatchery-reared individuals having a deeper body (in particular in the head and trunk regions), narrower caudal peduncles, and higher condition factor, as compared to wild conspecifics. Hatchery-reared marbled rockfish also had relatively shorter fins, for a given size. In terms of swimming performance, the hatchery-reared marbled rockfish performed worse than the wild, with slower burst swimming speeds and poorer endurance. Wild rockfish had higher body protein content but lower lipid levels compared to the hatchery-reared individuals. These results suggest that hatchery rearing conditions have a great impact on the phenotypic development, with possibly high effects on their post-release performance of the hatchery-reared marbled rockfish. Modifications for the hatchery environment and operation should be investigated with an aim to minimize the divergence in phenotypic development for production of more wild-like fish for stocking.

Bursting TENS increases walking endurance more than continuous TENS in middle-aged adults

The application of transcutaneous electrical nerve stimulation (TENS) can improve motor performance in both healthy individuals and those who present with clinically detectable sensory impairments. The purpose of our study was to compare the influence of continuous and intermittent TENS applied to the anterior thigh and tibialis anterior muscles on walking endurance and kinematics in healthy, middle-aged adults. Twenty-seven participants completed 4 trials of the 6-min walk test: Baseline, Continuous TENS (0.2 ms pulses at 50 Hz), Fast burst TENS (seven 0.15 ms pulses in 5 Hz bursts), and Slow burst TENS (seven 0.15 ms pulses in 0.5 Hz bursts). Linear mixed-effects models revealed that participants walked further (p ≤ 0.046) during all three TENS trials compared with Baseline (560 ± 76 m) and that they walked even further during both burst TENS trials (576 ± 83 m and 576 ± 83 m) compared with Continuous TENS (566 ± 79 m). Increases in walking speed were predicted by increases in stride length (p < 0.001) and stride frequency (p < 0.001) with toe-off angle being the only significant predictor (p ≤ 0.013) of both kinematic variables for the increase in walking speed. Bursting TENS was more effective than Continuous TENS at improving walking endurance in middle-aged, healthy adults.

Modulation of pacemaker channel function in a model of thalamocortical hyperexcitability by demyelination and cytokines.

A consensus is yet to be reached regarding the exact prevalence of epileptic seizures or epilepsy in multiple sclerosis (MS). In addition, the underlying pathophysiological basis of the reciprocal interaction among neuroinflammation, demyelination, and epilepsy remains unclear. Therefore, a better understanding of cellular and network mechanisms linking these pathologies is needed. Cuprizone-induced general demyelination in rodents is a valuable model for studying MS pathologies. Here, we studied the relationship among epileptic activity, loss of myelin, and pro-inflammatory cytokines by inducing acute, generalized demyelination in a genetic mouse model of human absence epilepsy, C3H/HeJ mice. Both cellular and network mechanisms were studied using in vivo and in vitro electrophysiological techniques. We found that acute, generalized demyelination in C3H/HeJ mice resulted in a lower number of spike–wave discharges, increased cortical theta oscillations, and reduction of slow rhythmic intrathalamic burst activity. In addition, generalized demyelination resulted in a significant reduction in the amplitude of the hyperpolarization-activated inward current (Ih) in thalamic relay cells, which was accompanied by lower surface expression of hyperpolarization-activated, cyclic nucleotide-gated channels, and the phosphorylated form of TRIP8b (pS237-TRIP8b). We suggest that demyelination-related changes in thalamic Ih may be one of the factors defining the prevalence of seizures in MS.

Antibacterial and osteogenic activities of clindamycin-releasing mesoporous silica/carboxymethyl chitosan composite hydrogels.

Conventional treatment of jaw bone infection is often ineffective at controlling bacterial infection and enhancing bone regeneration. Biodegradable composite hydrogels comprised of carboxymethyl chitosan (CMCS) and clindamycin (CDM)-loaded mesoporous silica nanoparticles (MCM-41), possessing dual antibacterial activity and osteogenic potency, were developed in the present study. CDM was successfully loaded into both untreated and plasma-treated MCM-41 nanoparticles, denoted as (p)-MCM-41, followed by the incorporation of each of CDM-loaded (p)-MCM-41 into CMCS. The resulting CDM-loaded composite hydrogels, (p)-MCM-41-CDM-CMCS, demonstrated slow degradation rates (about 70% remaining weight after 14-day immersion), while the CDM-free composite hydrogel entirely disintegrated after 4-day immersion. The plasma treatment was found to improve drug loading capacity and slow down initial drug burst effect. The prolonged releases of CDM from both (p)-MCM-41-CDM-CMCS retained their antibacterial effect against Streptococcus sanguinis for at least 14 days in vitro. In vitro assessment of osteogenic activity showed that the CDM-incorporated composite hydrogel was cytocompatible to human mesenchymal stem cells (hMSCs) and induced hMSC mineralization via p38-dependent upregulated alkaline phosphatase activity. In conclusion, novel (p)-MCM-41-CDM-CMCS hydrogels with combined controlled release of CDM and osteogenic potency were successfully developed for the first time, suggesting their potential clinical benefit for treatment of intraoral bone infection.

Should Governments Respond to Suspected Emotion-Driven Policy Bubbles? If Yes, How? If Not, Why Not?

In this paper, I elaborate on three strategies that governments can implement when faced with emotion-driven policy bubbles: the wait-and-see approach, the emotional containment approach, and the bubble-pricking approach. Based on the limited but important literature on this phenomenon and on studies addressing universal psychological processes, I offer some thoughts on the conditions under which each of these policy prescriptions may be the appropriate path to follow. I conclude that the case for a wait-and-see approach is strong, among other instances, when bubbles cannot be detected with a reasonable level of confidence while they are still in the initial overinvestment phase; the case for emotional containment is strong when policymakers are interested in preventing such a bubble from getting out of hand; and the case for the bubble-pricking approach is strong when (i) the growth of an emotion-driven policy bubble causes significant harm, and (ii) governments do not have at their disposal the necessary tools to keep the harmful effects of the policy bubble and its slow burst at a manageable level. Policymakers should also tailor their response to the particular characteristics of the policy bubble at hand and to the affective processes sustaining it.

The geometry of rest\u2013spike bistability

Morris–Lecar model is arguably the simplest dynamical model that retains both the slow–fast geometry of excitable phase portraits and the physiological interpretation of a conductance-based model. We augment this model with one slow inward current to capture the additional property of bistability between a resting state and a spiking limit cycle for a range of input current. The resulting dynamical system is a core structure for many dynamical phenomena such as slow spiking and bursting. We show how the proposed model combines physiological interpretation and mathematical tractability and we discuss the benefits of the proposed approach with respect to alternative models in the literature.

High-Resolution Mapping of Intestinal Spike Bursts and Motility.

Gastrointestinal (GI) motility and functional disorders affect up to 25% of the American population. Electrophysiological studies had shown a link between these functional motility disorders and abnormalities in GI bioelectrical activity. However, the dynamics between GI electrical activity (slow waves and spike bursts) and motility are not well understood. This study presents a framework to simultaneously record and quantify GI spike bursts and motility in vivo, in high-resolution. The dynamics between spike burst events and motility observed in 4 pig studies were investigated. A clear connection between spike burst patches and localized contractions was observed. The dataset consisted of 685 spike burst events in 191 patches. Contractions were associated with 81 patches. Spike burst patches associated with contractions had significantly higher amplitude, duration, and size compared to the ones that did not show an association. The amplitude, duration, and size of spike burst patches were positively correlated with the contraction strength. The spike burst patch energy displayed the highest correlation (r = 0.74). The contraction strength had a linear trend with spike burst patch energy. However, it could only account for 52% of the variance in contraction strength.

Phantom bursting may underlie electrical bursting in single pancreatic [formula omitted]-cells

Insulin is secreted by pancreatic β-cellsthat are electrically coupled into micro-organs called islets of Langerhans. The secretion is due to the influx of Ca2+ions that accompany electrical impulses, which are clustered into bursts. So-called “medium bursting” occurs in many β-cellsin intact islets, while in other islets the β-cellsexhibit “slow bursting”, with a much longer period. Each burst brings in Ca2+ that, through exocytosis, results in insulin secretion. When isolated from an islet, β-cellsbehave very differently. The electrical activity is much noisier, and consists primarily of trains of irregularly-timed spikes, or fast or slow bursting. Medium bursting, so often seen in intact islets, is rarely if ever observed. In this study, we examine what the isolated cell behavior can tell us about the mechanism for bursting in intact islets. A previous mathematical study concluded that the slow bursting observed in isolated β-cells, and therefore most likely in islets, must be due to intrinsic glycolytic oscillations, since this mechanism for bursting is robust to noise. It was demonstrated that an alternate mechanism, phantom bursting, was very sensitive to noise, and therefore could not account for the slow bursting in single cells. We re-examine these conclusions, motivated by recent experimental and mathematical modeling evidence that slow bursting in intact islets is, at least in many cases, driven by the phantom bursting mechanism and not endogenous glycolytic oscillations. We employ two phantom bursting models, one minimal and the other more biophysical, to determine the sensitivity of medium and slow bursting to electrical current noise. In the minimal model, both forms of bursting are highly sensitive to noise. In the biophysical model, while medium bursting is sensitive to noise, slow bursting is much less sensitive. This suggests that the slow bursting seen in isolated β-cellsmay be due to a phantom bursting mechanism, and by extension, slow bursting in intact islets may also be driven by this mechanism.