The effective use of blebbistatin to study the action potential of cardiac pacemaker cells of zebrafish (Danio rerio) during incremental warming

Marchant, James; Frank, Marina; Anthony, P. Farrell

doi:10.1016/j.crphys.2022.01.002

Cited by 4 publications

(1 citation statement)

References 40 publications

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“…Strikingly, previous research highlighted that blebbistatin can precipitate, blocking myocardial microvasculature and thereby inducing ischaemia and metabolic changes (Swift et al, 2012). In addition, a prolonging effect of blebbistatin on repolarization has been described in isolated hearts from rabbit (Brack et al, 2013) and pig (Lee et al, 2019), although other studies report no impact of blebbistatin on AP parameters (Fedorov et al, 2007;Marchant, et al, 2022). We here provide evidence of a time-dependent impact of high-dose blebbistatin on activation and repolarization kinetics in intact mouse hearts.…”

Section: Blebbistatin Time Effectmentioning

confidence: 99%

Optogenetic manipulation of cardiac repolarization gradients using sub-threshold illumination

et al. 2023

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Introduction: Mechanisms underlying cardiac arrhythmias are typically driven by abnormalities in cardiac conduction and/or heterogeneities in repolarization time (RT) across the heart. While conduction slowing can be caused by either electrophysiological defects or physical blockade in cardiac tissue, RT heterogeneities are mainly related to action potential (AP) prolongation or abbreviation in specific areas of the heart. Importantly, the size of the area with altered RT and the difference between the short RT and long RT (RT gradient) have been identified as critical determinators of arrhythmogenicity. However, current experimental methods for manipulating RT gradient rely on the use of ion channel inhibitors, which lack spatial and temporal specificity and are commonly only partially reversible. Therefore, the conditions facilitating sustained arrhythmia upon the presence of RT heterogeneities and/or defects in cardiac conduction remain to be elucidated.Methods: We here employ an approach based on optogenetic stimulation in a low-intensity fashion (sub-threshold illumination), to selectively manipulate cardiac electrical activity in defined areas of the heart.Results: As previously described, subthreshold illumination is a robust tool able to prolong action potentials (AP), decrease upstroke velocity as well as slow cardiac conduction, in a fully reversible manner. By applying a patterned sub-threshold illumination in intact mouse hearts constitutively expressing the light-gated ion channel channelrhodopsin-2 (ChR2), we optically manipulate RT gradients and cardiac conduction across the heart in a spatially selective manner. Moreover, in a proof-of-concept assessment we found that in the presence of patterned sub-threshold illumination, mouse hearts were more susceptible to arrhythmias. Hence, this optogenetic-based approach may be able to mimic conduction slowing and RT heterogeneities present in pathophysiological conditions.

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Section: Blebbistatin Time Effectmentioning

confidence: 99%

Optogenetic manipulation of cardiac repolarization gradients using sub-threshold illumination

et al. 2023

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Alterations in the axon initial segment plasticity is involved in early pathogenesis in Alzheimer's disease

Li,

Wang,

Wang

et al. 2024

MedComm

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Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, characterized by the early presence of amyloid‐β (Aβ) and hyperphosphorylated tau. Identifying the neuropathological changes preceding cognitive decline is crucial for early intervention. Axon initial segment (AIS) maintains the orderly structure of the axon and is responsible for initiating action potentials (APs). To investigate the role of AIS in early stages of AD pathogenesis, we focused on alterations in the AIS of neurons from APP/PS1 mouse models harboring familial AD mutations. AIS length and electrophysiological properties were assessed in neurons using immunostaining and patch‐clamp techniques. The expression and function of ankyrin G (AnkG) isoforms were evaluated by western blot and rescue experiments. We observed a significant shortening of AIS in APP/PS1 mice, which correlated with impaired action potential propagation. Furthermore, a decrease in the 480 kDa isoform of AnkG was observed. Rescue of this isoform restored AIS plasticity and improved long‐term potentiation in APP/PS1 neurons. Our study implicates AIS plasticity alterations and AnkG dysregulation as early events in AD. The restoration of AIS integrity by the 480 kDa AnkG isoform presents a potential therapeutic strategy for AD, underscoring the importance of targeting AIS stability in neurodegenerative diseases.

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Can Blebbistatin block the hypertrophy status in the zebrafish ex vivo cardiac model?

Bonvissuto

Ceci

Lauri

et al. 2022

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The effective use of blebbistatin to study the action potential of cardiac pacemaker cells of zebrafish (Danio rerio) during incremental warming

Cited by 4 publications

References 40 publications

Optogenetic manipulation of cardiac repolarization gradients using sub-threshold illumination

Optogenetic manipulation of cardiac repolarization gradients using sub-threshold illumination

Alterations in the axon initial segment plasticity is involved in early pathogenesis in Alzheimer's disease

Can Blebbistatin block the hypertrophy status in the zebrafish ex vivo cardiac model?

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