Overexpression of Sarcoendoplasmic Reticulum Calcium ATPase 2a Promotes Cardiac Sympathetic Neurotransmission via Abnormal Endoplasmic Reticulum and Mitochondria Ca
            <sup>2+</sup>
            Regulation

Shanks, Julia; Herring, Neil; Johnson, Errin; K, Liu; Li, Dan; Paterson, David J.

doi:10.1161/hypertensionaha.116.08507

Cited by 9 publications

(8 citation statements)

References 49 publications

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“…4A) when compared with neurons transfected with the empty vector. Furthermore, stellate neurons from SHRs have a greater ER calcium load and greater abundance of ER per unit cell volume compared to normal neurons [65]. These results are consistent with previous observations in superior cervical ganglia neurons from young prehypertensive SHR [25].…”

Section: Dysregulation Of Endoplasmic Reticulum In Presynaptic Neuronssupporting

confidence: 92%

“…The ER harbors the largest surface area of all eukaryotic organelles, and may represent up to 10 times the surface area of the plasma membrane [64]. Indeed, transmission electron microscopy images from stellate ganglia of 4-weekold SHR and WKY rats shows a striking difference in ER structure and organization [65]. In SHR rats, the ER is organized into spatially compact sheets compared with the more disperse and varied ER form observed in WKY neurons, suggesting that structural changes in neurons might underpin ER Ca 2+ handling differences observed cellular phenotypes.…”

Section: Dysregulation Of Endoplasmic Reticulum In Presynaptic Neuronsmentioning

confidence: 99%

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Pre-synaptic sympathetic calcium channels, cyclic nucleotide-coupled phosphodiesterases and cardiac excitability

Paterson

2019

Seminars in Cell & Developmental Biology

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In sympathetic neurons innervating the heart, action potentials activate voltage-gated Ca 2+ channels and evoke Ca 2+ entry into presynaptic terminals triggering neurotransmitter release. Binding of transmitters to specific receptors stimulates signal transduction pathways that cause changes in cardiac function. The mechanisms contributing to presynaptic Ca 2+ dynamics involve regulation of endogenous Ca 2+ buffers, in particular the endoplasmic reticulum, mitochondria and cyclic nucleotide targeted pathways. The purpose of this review is to summarize and highlight recent findings about Ca 2+ homeostasis in cardiac sympathetic neurons and how modulation of second messengers can drive neurotransmission and affect myocyte excitability in cardiovascular disease. Moreover, we discuss the underlying mechanism of abnormal intracellular Ca 2+ homeostasis and signaling in these neurons, and speculate on the role of phosphodiesterases as a therapeutic target to restore normal autonomic transmission in disease states of overactivity.

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Section: Dysregulation Of Endoplasmic Reticulum In Presynaptic Neuronssupporting

confidence: 92%

Section: Dysregulation Of Endoplasmic Reticulum In Presynaptic Neuronsmentioning

confidence: 99%

Pre-synaptic sympathetic calcium channels, cyclic nucleotide-coupled phosphodiesterases and cardiac excitability

Paterson

2019

Seminars in Cell & Developmental Biology

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“…In this context, perspectives of molecular treatment of HF appear. The demonstration that enzymes, such as the sarcoendoplasmic reticulum calcium ATPase 2a, associated with the development of HF in cytomegalovirus infections, promote sympathetic neuronal hyperactivation, with consequent greater sympathetic excitation in the cardiomyocyte (Shanks et al, 2017), indicates the importance of understanding this interaction. Although it is not a recent knowledge, the action of adenosine triphosphate (ATP), released by neurons, together with noradrenaline, as co-transmitters also plays a fundamental role in intercellular communication and is also an important perspective in the understanding not only of heart diseases, but also vascular diseases (Burnstock, 2017).…”

Section: Discussionmentioning

confidence: 99%

Conditioned medium of sympathetic ganglia with addition of fibroblast growth factor 2 promotes plasticity of cardiomyocytes in culture

Júnior¹,

Véras²,

Costa³

et al. 2019

JPCBS

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Introduction: The cardiac muscle cell, also called the cardiomyocyte, has specialized functions, playing a fundamental role in maintaining life, since it is responsible for the electrical and contractile activity of the heart. Like other specialized cells, it does not have an effective capacity for regeneration and its death or apoptosis is always an undesirable event, with sometimes catastrophic consequences, such as in Heart Failure (HF), which is known as the "final path" of heart diseases. Howe-Conditioned medium of sympathetic ganglia with addition of fibroblast growth factor 2 promotes plasticity of cardiomyocytes in culture

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“…Sections of approximately 100 μm were cut in the longitudinal plane, using a vibratome (Leica VT1200 S Vibratome). Samples were post-fixed in osmium tetroxide in 0.1 M cacodylate buffer, then washed and incubated in aqueous uranyl acetate (Shanks et al , 2017). Samples were dehydrated in a graded ethanol series and infiltrated with epoxy resin, using a Leica EM AMW automatic microwave tissue processor (Leicam Microsystems Inc.).…”

Section: Methodsmentioning

confidence: 99%

β2-Adrenergic receptor agonists ameliorate the adverse effect of long-term pyridostigmine on neuromuscular junction structure

Vanhaesebrouck

Webster

Maxwell

et al. 2019

Brain

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Acetylcholine receptor deficiency is the most common form of the congenital myasthenic syndromes, a heterogeneous collection of genetic disorders of neuromuscular transmission characterized by fatiguable muscle weakness. Most patients with acetylcholine receptor deficiency respond well to acetylcholinesterase inhibitors; however, in some cases the efficacy of acetylcholinesterase inhibitors diminishes over time. Patients with acetylcholine receptor deficiency can also benefit from the addition of a β2-adrenergic receptor agonist to their medication. The working mechanism of β2-adrenergic agonists in myasthenic patients is not fully understood. Here, we report the long-term follow-up for the addition of β2-adrenergic agonists for a cohort of patients with acetylcholine receptor deficiency on anticholinesterase medication that demonstrates a sustained quantitative improvement. Coincidently we used a disease model to mirror the treatment of acetylcholine receptor deficiency, and demonstrate improved muscle fatigue, improved neuromuscular transmission and improved synaptic structure resulting from the addition of the β2-adrenergic agonist salbutamol to the anticholinesterase medication pyridostigmine. Following an initial improvement in muscle fatiguability, a gradual decline in the effect of pyridostigmine was observed in mice treated with pyridostigmine alone (P < 0.001). Combination therapy with pyridostigmine and salbutamol counteracted this decline (P < 0.001). Studies of compound muscle action potential decrement at high nerve stimulation frequencies (P < 0.05) and miniature end-plate potential amplitude analysis (P < 0.01) showed an improvement in mice following combination therapy, compared to pyridostigmine monotherapy. Pyridostigmine alone reduced postsynaptic areas (P < 0.001) and postsynaptic folding (P < 0.01). Combination therapy increased postsynaptic area (P < 0.001) and promoted the formation of postsynaptic junctional folds (P < 0.001), in particular in fast-twitch muscles. In conclusion, we demonstrate for the first time how the improvement seen in patients from adding salbutamol to their medication can be explained in an experimental model of acetylcholine receptor deficiency, the most common form of congenital myasthenic syndrome. Salbutamol enhances neuromuscular junction synaptic structure by counteracting the detrimental effects of long-term acetylcholinesterase inhibitors on the postsynaptic neuromuscular junction. The results have implications for both autoimmune and genetic myasthenias where anticholinesterase medication is a standard treatment.

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Overexpression of Sarcoendoplasmic Reticulum Calcium ATPase 2a Promotes Cardiac Sympathetic Neurotransmission via Abnormal Endoplasmic Reticulum and Mitochondria Ca ²⁺ Regulation

Abstract: Supplemental Digital Content is available in the text.

Cited by 9 publications

References 49 publications

Pre-synaptic sympathetic calcium channels, cyclic nucleotide-coupled phosphodiesterases and cardiac excitability

Pre-synaptic sympathetic calcium channels, cyclic nucleotide-coupled phosphodiesterases and cardiac excitability

Conditioned medium of sympathetic ganglia with addition of fibroblast growth factor 2 promotes plasticity of cardiomyocytes in culture

β2-Adrenergic receptor agonists ameliorate the adverse effect of long-term pyridostigmine on neuromuscular junction structure

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Overexpression of Sarcoendoplasmic Reticulum Calcium ATPase 2a Promotes Cardiac Sympathetic Neurotransmission via Abnormal Endoplasmic Reticulum and Mitochondria Ca 2+ Regulation

Abstract: Supplemental Digital Content is available in the text.

Cited by 9 publications

References 49 publications

Pre-synaptic sympathetic calcium channels, cyclic nucleotide-coupled phosphodiesterases and cardiac excitability

Pre-synaptic sympathetic calcium channels, cyclic nucleotide-coupled phosphodiesterases and cardiac excitability

Conditioned medium of sympathetic ganglia with addition of fibroblast growth factor 2 promotes plasticity of cardiomyocytes in culture

β2-Adrenergic receptor agonists ameliorate the adverse effect of long-term pyridostigmine on neuromuscular junction structure

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Overexpression of Sarcoendoplasmic Reticulum Calcium ATPase 2a Promotes Cardiac Sympathetic Neurotransmission via Abnormal Endoplasmic Reticulum and Mitochondria Ca ²⁺ Regulation