scholarly journals Three C-terminal residues from the sulphonylurea receptor contribute to the functional coupling between the KATPchannel subunits SUR2A and Kir6.2

2008 ◽  
Vol 586 (13) ◽  
pp. 3075-3085 ◽  
Author(s):  
Julien P. Dupuis ◽  
Jean Revilloud ◽  
Christophe J. Moreau ◽  
Michel Vivaudou
Keyword(s):  
Functional Coupling ◽  
Sulphonylurea Receptor

Site-Specific Protein Covalent Attachment to Nanotubes and Its Electronic Impact on Single Molecule Function

2019 ◽  
Author(s):  
Adam Beachey ◽  
Harley Worthy ◽  
William David Jamieson ◽  
Suzanne Thomas ◽  
Benjamin Bowen ◽  
...  
Keyword(s):  
Single Molecule ◽  
Fluorescent Protein ◽  
Functional Integration ◽  
Attachment Site ◽  
Covalent Attachment ◽  
Great Promise ◽  
Functional Coupling ◽  
Phenyl Azide ◽  
Electronic Impact ◽  
Protein Attachment

<p>Functional integration of proteins with carbon-based nanomaterials such as nanotubes holds great promise in emerging electronic and optoelectronic applications. Control over protein attachment poses a major challenge for consistent and useful device fabrication, especially when utilizing single/few molecule properties. Here, we exploit genetically encoded phenyl azide photochemistry to define the direct covalent attachment of three different proteins, including the fluorescent protein GFP, to carbon nanotube side walls. Single molecule fluorescence revealed that on attachment to SWCNTs GFP’s fluorescence changed in terms of intensity and improved resistance to photobleaching; essentially GFP is fluorescent for much longer on attachment. The site of attachment proved important in terms of electronic impact on GFP function, with the attachment site furthest from the functional center having the larger effect on fluorescence. Our approach provides a versatile and general method for generating intimate protein-CNT hybrid bioconjugates. It can be potentially applied easily to any protein of choice; attachment position and thus interface characteristics with the CNT can easily be changed by simply placing the phenyl azide chemistry at different residues by gene mutagenesis. Thus, our approach will allow consistent construction and modulate functional coupling through changing the protein attachment position.</p>

Slow skeletal muscle myosin-binding protein-C (MyBPC1) mediates recruitment of muscle-type creatine kinase (CK) to myosin

2011 ◽  
Vol 436 (2) ◽  
pp. 437-445 ◽  
Author(s):  
Zhe Chen ◽  
Tong-Jin Zhao ◽  
Jie Li ◽  
Yan-Song Gao ◽  
Fan-Guo Meng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Muscle Contraction ◽  
Binding Protein ◽  
High Energy ◽  
Functional Coupling ◽  
Muscle Type ◽  
Myosin Binding Protein ◽  
Slow Skeletal Muscle ◽  
Myosin Binding

Muscle contraction requires high energy fluxes, which are supplied by MM-CK (muscle-type creatine kinase) which couples to the myofibril. However, little is known about the detailed molecular mechanisms of how MM-CK participates in and is regulated during muscle contraction. In the present study, MM-CK is found to physically interact with the slow skeletal muscle-type MyBPC1 (myosin-binding protein C1). The interaction between MyBPC1 and MM-CK depended on the creatine concentration in a dose-dependent manner, but not on ATP, ADP or phosphocreatine. The MyBPC1–CK interaction favoured acidic conditions, and the two molecules dissociated at above pH 7.5. Domain-mapping experiments indicated that MM-CK binds to the C-terminal domains of MyBPC1, which is also the binding site of myosin. The functional coupling of myosin, MyBPC1 and MM-CK is further corroborated using an ATPase activity assay in which ATP expenditure accelerates upon the association of the three proteins, and the apparent Km value of myosin is therefore reduced. The results of the present study suggest that MyBPC1 acts as an adaptor to connect the ATP consumer (myosin) and the regenerator (MM-CK) for efficient energy metabolism and homoeostasis.

scholarly journals In vivo glucose metabolism and glutamate levels in mGluR5 knockout mice: a multimodal neuroimaging study using [18F]FDG microPET and MRS

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yo-Han Joo ◽  
Yun-Kwan Kim ◽  
In-Gyu Choi ◽  
Hyeon-Jin Kim ◽  
Young-Don Son ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Glucose Metabolism ◽  
Cerebral Glucose Metabolism ◽  
Functional Coupling ◽  
Resonance Spectroscopy ◽  
Acute Administration ◽  
Multimodal Neuroimaging ◽  
Mk 801 ◽  
Genetic Ablation ◽  
Neuroimaging Study

Abstract Background Perturbed functional coupling between the metabotropic glutamate receptor-5 (mGluR5) and N-methyl-d-aspartate (NMDA) receptor-mediated excitatory glutamatergic neurotransmission may contribute to the pathophysiology of psychiatric disorders such as schizophrenia. We aimed to establish the functional interaction between mGluR5 and NMDA receptors in brain of mice with genetic ablation of the mGluR5. Methods We first measured the brain glutamate levels with magnetic resonance spectroscopy (MRS) in mGluR5 knockout (KO) and wild-type (WT) mice. Then, we assessed brain glucose metabolism with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography before and after the acute administration of an NMDA antagonist, MK-801 (0.5 mg/kg), in the same mGluR5 KO and WT mice. Results Between-group comparisons showed no significant differences in [18F]FDG standardized uptake values (SUVs) in brain of mGluR5 KO and WT mice at baseline, but widespread reductions in mGluR5 KO mice compared to WT mice after MK-801 administration (p < 0.05). The baseline glutamate levels did not differ significantly between the two groups. However, there were significant negative correlations between baseline prefrontal glutamate levels and regional [18F]FDG SUVs in mGluR5 KO mice (p < 0.05), but no such correlations in WT mice. Fisher’s Z-transformation analysis revealed significant between-group differences in these correlations (p < 0.05). Conclusions This is the first multimodal neuroimaging study in mGluR5 KO mice and the first report on the association between cerebral glucose metabolism and glutamate levels in living rodents. The results indicate that mGluR5 KO mice respond to NMDA antagonism with reduced cerebral glucose metabolism, suggesting that mGluR5 transmission normally moderates the net effects of NMDA receptor antagonism on neuronal activity. The negative correlation between glutamate levels and glucose metabolism in mGluR5 KO mice at baseline may suggest an unmasking of an inhibitory component of the glutamatergic regulation of neuronal energy metabolism.

scholarly journals Effects of transcranial static magnetic stimulation over the primary motor cortex on local and network spontaneous electroencephalogram oscillations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sumiya Shibata ◽  
Tatsunori Watanabe ◽  
Yoshihiro Yukawa ◽  
Masatoshi Minakuchi ◽  
Ryota Shimomura ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Power Spectrum ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Cortical Excitability ◽  
Controlled Study ◽  
Functional Coupling ◽  
Phase Lag ◽  
Theta Band ◽  
Double Blind

AbstractTranscranial static magnetic stimulation (tSMS) is a novel non-invasive brain stimulation technique that reduces cortical excitability at the stimulation site. We investigated the effects of tSMS over the left primary motor cortex (M1) for 20 min on the local electroencephalogram (EEG) power spectrum and interregional EEG coupling. Twelve right-handed healthy subjects participated in this crossover, double-blind, sham-controlled study. Resting-state EEG data were recorded for 3 min before the intervention and 17 min after the beginning of the intervention. The power spectrum at the left central electrode (C3) and the weighted phase lag index (wPLI) between C3 and the other electrodes was calculated for theta (4–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz) frequencies. The tSMS significantly increased theta power at C3 and the functional coupling in the theta band between C3 and the parietal midline electrodes. The tSMS over the left M1 for 20 min exhibited modulatory effects on local cortical activity and interregional functional coupling in the theta band. The neural oscillations in the theta band may have an important role in the neurophysiological effects induced by tSMS over the frontal cortex.

A human airway smooth muscle cell line that retains physiological responsiveness

1989 ◽  
Vol 256 (2) ◽  
pp. C329-C335 ◽  
Author(s):  
R. A. Panettieri ◽  
R. K. Murray ◽  
L. R. DePalo ◽  
P. A. Yadvish ◽  
M. I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Cell Line ◽  
Airway Smooth Muscle ◽  
Cytosolic Calcium ◽  
Airway Smooth Muscle Cell ◽  
Airway Smooth Muscle Cells ◽  
Functional Coupling ◽  
Functional Responses ◽  
Human Airway Smooth Muscle ◽  
Human Airway

We report the development of a nontransformed line of human airway smooth muscle cells retaining smooth muscle-specific contractile protein expression and physiological responsiveness to agonists implicated in inflammatory airway diseases. Specific responses to histamine, leukotrienes, bradykinin, platelet-activating factor, substance P, and thromboxane analogues are demonstrated as well as functional coupling to beta-adrenergic receptors. The cell line was characterized using indirect immunofluorescence, as well as electrophoretic separation and immunoblot analysis of smooth muscle-specific actin. Functional responses were assessed by measurements of cytosolic calcium and stimulation of adenosine 3',5'-cyclic monophosphate production. The cells retain their responsiveness over many population doublings and should be a useful model to examine specific receptor-effector mechanisms, as well as the effects of neurohumoral agents on the regulation of airway smooth muscle growth and differentiation.

scholarly journals Reduced resting state functional connectivity with increasing age-related hearing loss and McGurk susceptibility

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alina Schulte ◽  
Christiane M. Thiel ◽  
Anja Gieseler ◽  
Maike Tahden ◽  
Hans Colonius ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Functional Connectivity ◽  
Resting State ◽  
Mcgurk Effect ◽  
Functional Coupling ◽  
Resting State Functional Connectivity ◽  
Visual Integration ◽  
Age Related ◽  
Hearing Thresholds ◽  
Age Related Hearing Loss

Abstract Age-related hearing loss has been related to a compensatory increase in audio-visual integration and neural reorganization including alterations in functional resting state connectivity. How these two changes are linked in elderly listeners is unclear. The current study explored modulatory effects of hearing thresholds and audio-visual integration on resting state functional connectivity. We analysed a large set of resting state data of 65 elderly participants with a widely varying degree of untreated hearing loss. Audio-visual integration, as gauged with the McGurk effect, increased with progressing hearing thresholds. On the neural level, McGurk illusions were negatively related to functional coupling between motor and auditory regions. Similarly, connectivity of the dorsal attention network to sensorimotor and primary motor cortices was reduced with increasing hearing loss. The same effect was obtained for connectivity between the salience network and visual cortex. Our findings suggest that with progressing untreated age-related hearing loss, functional coupling at rest declines, affecting connectivity of brain networks and areas associated with attentional, visual, sensorimotor and motor processes. Especially connectivity reductions between auditory and motor areas were related to stronger audio-visual integration found with increasing hearing loss.

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