Phantom bursting may underlie electrical bursting in single pancreatic<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si183.svg"><mml:mrow><mml:mi>β</mml:mi></mml:mrow></mml:math>-cells

Fazli, Mehran; Vo, Theodore; Bertram, Richard

doi:10.1016/j.jtbi.2020.110346

Cited by 6 publications

(2 citation statements)

References 39 publications

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“…More specifically, the slow oscillations cause shifts in the frequency of the fast oscillations, but the average value of these fast oscillations is set by a glucose-dependent mechanism, distinct from the one responsible for slow oscillations. This corroborates the recent developments in computational models of beta cell activity, suggesting that the slow oscillations may originate from intrinsic mechanisms, in addition to Ca 2+ effects on the enzymes involved in beta cell metabolism (McKenna et al, 2016;Bertram et al, 2018;Fazli et al, 2020). We wish to point out that our method of measuring changes in Ca 2+ does not enable assessments of absolute changes in amplitudes and thus we cannot completely exclude the possibility that the amplitude of the slow oscillations may be glucose-dependent.…”

Section: Discussionsupporting

confidence: 79%

Assessing Different Temporal Scales of Calcium Dynamics in Networks of Beta Cell Populations

et al. 2021

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Beta cells within the pancreatic islets of Langerhans respond to stimulation with coherent oscillations of membrane potential and intracellular calcium concentration that presumably drive the pulsatile exocytosis of insulin. Their rhythmic activity is multimodal, resulting from networked feedback interactions of various oscillatory subsystems, such as the glycolytic, mitochondrial, and electrical/calcium components. How these oscillatory modules interact and affect the collective cellular activity, which is a prerequisite for proper hormone release, is incompletely understood. In the present work, we combined advanced confocal Ca2+ imaging in fresh mouse pancreas tissue slices with time series analysis and network science approaches to unveil the glucose-dependent characteristics of different oscillatory components on both the intra- and inter-cellular level. Our results reveal an interrelationship between the metabolically driven low-frequency component and the electrically driven high-frequency component, with the latter exhibiting the highest bursting rates around the peaks of the slow component and the lowest around the nadirs. Moreover, the activity, as well as the average synchronicity of the fast component, considerably increased with increasing stimulatory glucose concentration, whereas the stimulation level did not affect any of these parameters in the slow component domain. Remarkably, in both dynamical components, the average correlation decreased similarly with intercellular distance, which implies that intercellular communication affects the synchronicity of both types of oscillations. To explore the intra-islet synchronization patterns in more detail, we constructed functional connectivity maps. The subsequent comparison of network characteristics of different oscillatory components showed more locally clustered and segregated networks of fast oscillatory activity, while the slow oscillations were more global, resulting in several long-range connections and a more cohesive structure. Besides the structural differences, we found a relatively weak relationship between the fast and slow network layer, which suggests that different synchronization mechanisms shape the collective cellular activity in islets, a finding which has to be kept in mind in future studies employing different oscillations for constructing networks.

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Section: Discussionsupporting

confidence: 79%

Assessing Different Temporal Scales of Calcium Dynamics in Networks of Beta Cell Populations

et al. 2021

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“…Using slow-fast analysis, first introduced in [25,26], BPOs were classified based on their underlying dynamics [26][27][28][29][30], and later expanded in a recent study using canard theory [31]. The application of slow-fast analysis has been extended to many Hodgkin-Huxley type models describing the bursting dynamics of many neurophysiological and endocrine systems, including for example inner hair cells [32], embryonic pre-BötC neuron [33] and pancreatic β cells [34]. It provides a tool to determine how different time scales interact and how they are responsible in generating the bursting activity observed.…”

Section: Introductionmentioning

confidence: 99%

Bursting in cerebellar stellate cells induced by pharmacological agents: Non-sequential spike adding

et al. 2020

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Cerebellar stellate cells (CSCs) are spontaneously active, tonically firing (5-30 Hz), inhibitory interneurons that synapse onto Purkinje cells. We previously analyzed the excitability properties of CSCs, focusing on four key features: type I excitability, non-monotonic first-spike latency, switching in responsiveness and runup (i.e., temporal increase in excitability during whole-cell configuration). In this study, we extend this analysis by using whole-cell configuration to show that these neurons can also burst when treated with certain pharmacological agents separately or jointly. Indeed, treatment with 4-Aminopyridine (4-AP), a partial blocker of delayed rectifier and A-type K+ channels, at low doses induces a bursting profile in CSCs significantly different than that produced at high doses or when it is applied at low doses but with cadmium (Cd2+), a blocker of high voltage-activated (HVA) Ca2+ channels. By expanding a previously revised Hodgkin–Huxley type model, through the inclusion of Ca2+-activated K+ (K(Ca)) and HVA currents, we explain how these bursts are generated and what their underlying dynamics are. Specifically, we demonstrate that the expanded model preserves the four excitability features of CSCs, as well as captures their bursting patterns induced by 4-AP and Cd2+. Model investigation reveals that 4-AP is potentiating HVA, inducing square-wave bursting at low doses and pseudo-plateau bursting at high doses, whereas Cd2+ is potentiating K(Ca), inducing pseudo-plateau bursting when applied in combination with low doses of 4-AP. Using bifurcation analysis, we show that spike adding in square-wave bursts is non-sequential when gradually changing HVA and K(Ca) maximum conductances, delayed Hopf is responsible for generating the plateau segment within the active phase of pseudo-plateau bursts, and bursting can become “chaotic” when HVA and K(Ca) maximum conductances are made low and high, respectively. These results highlight the secondary effects of the drugs applied and suggest that CSCs have all the ingredients needed for bursting.

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Investigating the dynamics of bursting by combining two fast–slow analyses with codimension-2 bifurcations in the embryonic pre-BötC neuron model

Liu

Yang

2023

Nonlinear Dyn

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Phantom bursting may underlie electrical bursting in single pancreaticβ-cells

Cited by 6 publications

References 39 publications

Assessing Different Temporal Scales of Calcium Dynamics in Networks of Beta Cell Populations

Assessing Different Temporal Scales of Calcium Dynamics in Networks of Beta Cell Populations

Bursting in cerebellar stellate cells induced by pharmacological agents: Non-sequential spike adding

Investigating the dynamics of bursting by combining two fast–slow analyses with codimension-2 bifurcations in the embryonic pre-BötC neuron model

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