Dataset Information

Proteomics analysis of rat primary myocyte and neuron-myocyte co-cultures

ABSTRACT: Alterations in autonomic function are known to occur in cardiac conditions including sudden cardiac death. Cardiac stimulation via sympathetic neurons can potentially trigger arrhythmias. Dissecting direct neural-cardiac interactions at the cellular level is technically challenging and understudied due to the lack of experimental model systems and methodologies. Here we demonstrate the utility of optical interrogation of sympathetic neurons and their effects on macroscopic cardiomyocyte network dynamics to address research targets such as the effects of adrenergic stimulation via the release of neurotransmitters, the effect of neuronal numbers on cardiac wave behaviour and the applicability of optogenetics in mechanistic in vitro studies. We present novel methodologies to study neuron-cardiomyocyte interactions involving optogenetic selective probing and all-optical electrophysiology to measure electrical activity in an automated fashion, illustrating the power and high-throughput capability of such interrogations. We present new findings on how neurons impact cardiac macroscopic wave properties, the links between neuron density and cardiac firing rates as well as the challenges and benefits of macroscopic co-cultures as experimental model systems.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart, Cell Culture, Sympathetic Neuron, Cardiac Muscle Cell

SUBMITTER: Holger Kramer

LAB HEAD: Holger B R Kramer

PROVIDER: PXD019908 | Pride | 2020-07-21

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Holger_22-SD-myo_01-11-12_7days_09June2016.mgf	Mgf
	Holger_22-SD-myo_01-11-12_7days_09June2016.mzid.gz	Mzid
	Holger_22-SD-myo_01-11-12_7days_09June2016.raw	Raw
	Holger_22-SD-myo_01-11-12_7days_09June2016_DTASelect.txt	Txt
	Holger_22-SDCo_01-11-12_7days_09June2016.mgf	Mgf

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Publications

Optical Interrogation of Sympathetic Neuronal Effects on Macroscopic Cardiomyocyte Network Dynamics.

Burton Rebecca-Ann B RB Tomek Jakub J Ambrosi Christina M CM Larsen Hege E HE Sharkey Amy R AR Capel Rebecca A RA Corbett Alexander D AD Bilton Samuel S Klimas Aleksandra A Stephens Guy G Cremer Maegan M Bose Samuel J SJ Li Dan D Gallone Giuseppe G Herring Neil N Mann Edward O EO Kumar Abhinav A Kramer Holger H Entcheva Emilia E Paterson David J DJ Bub Gil G

iScience 20200701 7

Cardiac stimulation via sympathetic neurons can potentially trigger arrhythmias. We present approaches to study neuron-cardiomyocyte interactions involving optogenetic selective probing and all-optical electrophysiology to measure activity in an automated fashion. Here we demonstrate the utility of optical interrogation of sympathetic neurons and their effects on macroscopic cardiomyocyte network dynamics to address research targets such as the effects of adrenergic stimulation via the release o ...[more]

PMID: 32674058

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Project description:Maternal diabetes is a recognized risk factor for both short-term and long-term complications in offspring. Beyond the direct teratogenicity of maternal diabetes, the intrauterine environment can influence offspring cardiovascular health. Abnormalities in the cardiac sympathetic system are implicated in conditions such as sudden infant death syndrome, cardiac arrhythmic death, heart failure, and certain congenital heart defects in children from diabetic pregnancies. However, the mechanisms by which maternal diabetes affect the development of the cardiac sympathetic system and consequently, heightening health risks and predisposing to cardiovascular disease remain poorly understood. In this study, we present a comprehensive analysis of the combined impact of a Hif1a-deficient sympathetic system and the maternal diabetes environment on both heart development and the formation of the cardiac sympathetic system. The synergic negative effect of exposure to maternal diabetes and Hif1a deficiency resulted in the most pronounced deficit in cardiac sympathetic innervation and the development of adrenal medulla. Abnormalities in the cardiac sympathetic system were accompanied by a smaller heart, reduced ventricular wall thickness, dilated subepicardial veins, and coronary arteries in the myocardium, along with anomalies in the branching and connections of the main coronary arteries. Transcriptional profiling by RNA-seq revealed significant transcriptome changes in Hif1a-deficient sympathetic neurons, primarily associated with cell cycle regulation, proliferation, and mitosis, explaining the shrinkage of the sympathetic neuron population. Our data demonstrate that a failure to adequately activate HIF-1α regulatory pathway, particularly in the context of maternal diabetes, may contribute to abnormalities in the cardiac sympathetic system. In conclusion, our findings indicate that the interplay between deficiencies in the cardiac sympathetic system and subtle structural alternations in the vasculature, microvasculature, and myocardium during heart development not only increases the risk of cardiovascular disease but also diminishes the adaptability to the stress associated with the transition to extrauterine life, thus, increasing the risk of neonatal death.