Spatio-temporal concentration of acetylcholine in vertebrate synaptic cleft

Aidoo, Anthony Y.; Ward, Kim Y.

doi:10.1016/j.mcm.2006.03.003

Cited by 20 publications

(14 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three tyrosinase attachment sites surround each g-quadruplex dye intercalation site to maximize its interaction with PtTPFPP ( Figure 1 a). Tyrosinase produces localized changes in oxygen levels during dopamine oxidation [ 34 , 35 ]. Oxygen sensitive PtTPFPP responds to the local oxygen changes causing the sensor to “turn on” or increase its phosphorescence ( Figure 1 b).…”

Section: Resultsmentioning

confidence: 99%

Quadruplex Integrated DNA (QuID) Nanosensors for Monitoring Dopamine

Morales

Skipwith

Clark

2015

Sensors

View full text Add to dashboard Cite

Dopamine is widely innervated throughout the brain and critical for many cognitive and motor functions. Imbalances or loss in dopamine transmission underlie various psychiatric disorders and degenerative diseases. Research involving cellular studies and disease states would benefit from a tool for measuring dopamine transmission. Here we show a Quadruplex Integrated DNA (QuID) nanosensor platform for selective and dynamic detection of dopamine. This nanosensor exploits DNA technology and enzyme recognition systems to optically image dopamine levels. The DNA quadruplex architecture is designed to be compatible in physically constrained environments (110 nm) with high flexibility, homogeneity, and a lower detection limit of 110 µM.

show abstract

Section: Resultsmentioning

confidence: 99%

Quadruplex Integrated DNA (QuID) Nanosensors for Monitoring Dopamine

Morales

Skipwith

Clark

2015

Sensors

View full text Add to dashboard Cite

show abstract

“…The structure of Torpedo nAChR (PDB 6UWZ published in [ 20 ]) was used as a source of α1 nAChR extracellular domain atomic coordinates. Point mutations were introduced to positions 153 and 199 using UCSF Chimera “Rotamers” tool with the Dunbrack’s rotamer library [ 34 , 35 ]. The Gromos54a7 forcefield [ 36 ] was used in GROMACS 5.0.7 [ 37 ] to generate the topology and coordinates files.…”

Section: Methodsmentioning

confidence: 99%

Point Mutations of Nicotinic Receptor α1 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia

et al. 2021

View full text Add to dashboard Cite

Slow-channel congenital myasthenic syndromes (SCCMSs) are rare genetic diseases caused by mutations in muscle nicotinic acetylcholine receptor (nAChR) subunits. Most of the known SCCMS-associated mutations localize at the transmembrane region near the ion pore. Only two SCCMS point mutations are at the extracellular domains near the acetylcholine binding site, α1(G153S) being one of them. In this work, a combination of molecular dynamics, targeted mutagenesis, fluorescent Ca2+ imaging and patch-clamp electrophysiology has been applied to G153S mutant muscle nAChR to investigate the role of hydrogen bonds formed by Ser 153 with C-loop residues near the acetylcholine-binding site. Introduction of L199T mutation to the C-loop in the vicinity of Ser 153 changed hydrogen bonds distribution, decreased acetylcholine potency (EC50 2607 vs. 146 nM) of the double mutant and decay kinetics of acetylcholine-evoked cytoplasmic Ca2+ rise (τ 14.2 ± 0.3 vs. 34.0 ± 0.4 s). These results shed light on molecular mechanisms of nAChR activation-desensitization and on the involvement of such mechanisms in channelopathy genesis.

show abstract

“…Similar ISO doses (0.1–1 μM) have previously been used with guinea pig myocytes to induce early and delayed afterdepolarizations (Yamawake et al, 1992 ; De Ferrari et al, 1995 ). ACh physiological concentrations can range from the nanomolar in plasma (Fujii et al, 1995 ) to the millimolar at the neuromuscular junction (Aidoo and Ward, 2006 ), and therefore we chose a concentration that has been associated with augmented calcium handling in guinea pig myocytes (Song et al, 1998 ). In another set of experiments, the autonomic agonist (drug A) was perfused for 21 min, and then was followed by the addition of the other agonist (drug B, gray filled bar, Figure 1D ).…”

Section: Methodsmentioning

confidence: 99%

Temporal response of ectopic activity in guinea pig ventricular myocardium in response to isoproterenol and acetylcholine

Greer-Short

Poelzing

2015

Front. Physiol.

View full text Add to dashboard Cite

Both β adrenergic and muscarinic receptor stimulation independently potentiate arrhythmogenesis. However, the effect of simultaneous stimulation on arrhythmogenesis is not well known. The purpose of this study was to determine the temporal response of arrhythmia risk to individual and combined autonomic agonists. Guinea pig hearts were excised and Langendorff-perfused. The β adrenergic receptor and muscarinic receptor agonists were isoproterenol (ISO, 0.6 μM) and acetylcholine (ACh, 10 μM), respectively. All measurements with agonists occurred over 21 min. ISO induced ectopic activity for the first 8 min. ISO also transiently shortened and then prolonged R-R interval over a similar time course. ACh added after ISO transiently induced ectopic activity for 12 min, while R-R interval invariantly prolonged. ACh alone produced few ectopic beats, while invariantly prolonging R-R interval. In contrast to ISO alone, ISO following ACh significantly increased ectopic activity and shortened R-R interval for the duration of the experiment. Animals aged 17–19 months exhibited sustained arrhythmogenesis while those aged 11–14 did not. When ACh was removed in older hearts while ISO perfused, a transient increase in ectopic activity and decreased R-R interval was observed, similar to ISO alone. These data suggest that pre-treating with and maintaining ACh perfusion can sustain ISO sensitivity, in contrast to ISO perfusion alone.

show abstract

Spatio-temporal concentration of acetylcholine in vertebrate synaptic cleft

Cited by 20 publications

References 30 publications

Quadruplex Integrated DNA (QuID) Nanosensors for Monitoring Dopamine

Quadruplex Integrated DNA (QuID) Nanosensors for Monitoring Dopamine

Point Mutations of Nicotinic Receptor α1 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia

Temporal response of ectopic activity in guinea pig ventricular myocardium in response to isoproterenol and acetylcholine

Contact Info

Product

Resources

About