A classic experiment revisited: membrane permeability changes during the action potential

Powell, Carolyn L; Brown, Angus M.

doi:10.1152/advan.00188.2020

Cited by 11 publications

(5 citation statements)

References 17 publications

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“…7-Supplement 1A), which increased the spike AHP and slightly reduced spike height (Fig. 7A and B), as expected (Strauss et al, 2008; Yang and Huang, 2022; Bacak et al, 2016; Abdulla et al, 2021; Powell and Brown, 2021). In the model preBötC network with distributed spike heights ( g SPK = U (0, 12) nS ), decreasing [ K + ] ext from a baseline value of 8.5 mM reduced excitability as indicated by an increased g Tonic required for neurons to enter spiking/bursting modes (Fig.…”

Section: Resultssupporting

confidence: 82%

Interdependence of cellular and network properties in respiratory rhythmogenesis

Phillips,

Baertsch

2023

Preprint

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How breathing is generated by the preBötzinger Complex (preBötC) remains divided between two ideological frameworks, and the persistent sodium current (INaP) lies at the heart of this debate. AlthoughINaPis widely expressed, thepacemaker hypothesisconsiders it essential because it endows a small subset of neurons with intrinsic bursting or “pacemaker” activity. In contrast,burstlet theoryconsidersINaPdispensable because rhythm emerges from “pre-inspiratory” spiking activity driven by feed-forward network interactions. Using computational modeling, we discover that changes in spike shape can dissociateINaPfrom intrinsic bursting. Consistent with many experimental benchmarks, conditional effects on spike shape during simulated changes in oxygenation, development, extracellular potassium, and temperature alter the prevalence of intrinsic bursting and pre-inspiratory spiking without altering the role ofINaP. Our results support a unifying hypothesis whereINaPand excitatory network interactions, but not intrinsic bursting or pre-inspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.SIGNIFICANCE STATEMENTBreathing is a vital rhythmic process originating from the preBötzinger complex. Since its discovery in 1991, there has been a spirited debate about whether respiratory rhythm generation emerges as a network property or is driven by a subset of specialized neurons with rhythmic bursting capabilities, endowed by intrinsic currents. Here, using computational modeling, we propose a unifying data-driven model of respiratory rhythm generation which bridges the gap between these competing theories. In this model, both intrinsic cellular properties (a persistent sodium current) and network properties (recurrent excitation), but not intrinsic bursting, are essential and interdependent features of respiratory rhythm generation.

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Section: Resultssupporting

confidence: 82%

Interdependence of cellular and network properties in respiratory rhythmogenesis

Phillips,

Baertsch

2023

Preprint

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“…When comparing MCD neurons with control, we also found a shift to more depolarized threshold and larger AHP. Interestingly, Powell et al, 2021 illustrated recently that with an increase in extracellular concentration of [K+], AHP magnitude got bigger and threshold got slightly more depolarized 75 . It could therefore be there is more outflux of [K+] into the extracellular space because of the hyperexcitable cortical slice compared to control (Avoli et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Characterizing the diversity of L2/3 human neocortical neurons in epilepsy

Kushner

Hoffman

Brzezinski

et al. 2022

Preprint

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In the current study, we performed whole-cell current clamp recordings from human cortical neurons in layer 2/3 of the human neocortex in order to characterize the diversity of L2/3 human neocortical neurons in epileptic foci with various etiologies in order to begin to elucidate the underlying mechanisms of hyperexcitability which are still mostly unknown. We differentiated neuronal subtypes based on their firing patterns and AHP kinetics or epilepsy subtype (malformation of cortical development (MCD) vs. other (non-MCD)). We found that L2/3 pyramidal neurons have diverse firing properties and action potential kinetics, with some neurons looking remarkably similar to LTS interneurons. We also saw that L2/3 pyramidal neurons could be split into those with fast AHPs and those without, medium AHPs (mAHPs). Based on these parameters, we were unable to significantly differentiate neurons based on firing properties indicating that AHP component kinetics alone do not dictate L2/3 pyramidal neuron firing in human epileptic cortical slices. We also report significant differences in intrinsic properties between MCD and non-MCD and control L2/3 pyramidal neurons and are the first to characterize that wash on of the proconvulsant drug, 4-aminopyridine (4-AP), leads to increased AP duration, less firing rate (FR) accommodation, and slowed down AHPs. Overall, the present study is the first to characterize the large variability of L2/3 human neocortical pyramidal neurons, to compare between L2/3 pyramidal neurons within the epileptic foci between MCD and non-MCD cases, to use control tissue from tumor patients without incidence of seizure, and to determine the influence of 4-AP on L2/3 pyramidal neuron intrinsic properties.

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“…are not always experimentally measured but are determined so that the GHK eq. can reproduce the experimentally measured membrane potential [17][18][19][20]. Therefore, if the way to determine the numerical value of j i K described above is scientifically inappropriate, so is the prevailing procedure for finding the numerical value of i P from the GHK eq.…”

Section: Verification Of mentioning

confidence: 99%

Early confirmative work of the Association-Induction Hypothesis

Tamagawa

2024

MCMS

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A classic experiment revisited: membrane permeability changes during the action potential

Cited by 11 publications

References 17 publications

Interdependence of cellular and network properties in respiratory rhythmogenesis

Interdependence of cellular and network properties in respiratory rhythmogenesis

Characterizing the diversity of L2/3 human neocortical neurons in epilepsy

Early confirmative work of the Association-Induction Hypothesis

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