scholarly journals Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones

2006 ◽  
Vol 574 (3) ◽  
pp. 819-834 ◽  
Author(s):  
J. J. Kuo ◽  
R. H. Lee ◽  
L. Zhang ◽  
C. J. Heckman
Keyword(s):  
Essential Role ◽  
Sodium Current ◽  
Persistent Sodium Current ◽  
Spinal Neurones ◽  
Spike Initiation

scholarly journals It takes two to tango: M-current swings with the persistent sodium current to set the speed of locomotion

2020 ◽  
Author(s):  
Jeremy Verneuil ◽  
Cécile Brocard ◽  
Laurent Villard ◽  
Julie Peyronnet-Roux ◽  
Frédéric Brocard
Keyword(s):  
Computational Models ◽  
Sodium Current ◽  
Outward Current ◽  
Persistent Sodium Current ◽  
Pacemaker Neurons ◽  
Locomotor Rhythm ◽  
M Current ◽  
Frequency Regime ◽  
Locomotion Speed

SummaryThe central pattern generator (CPG) for locomotion is set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current (INaP). How they proceed to regulate the locomotor rhythm remained unknown. Here, in neonatal rodents, we identified a persistent potassium current, critical in regulating pacemakers and locomotion speed. This current recapitulates features of the M-current (IM); a subthreshold non-inactivating outward current blocked by XE991 and enhanced by ICA73. Immunostaining and mutant mice highlight an important role of axonal Kv7.2 channels in mediating IM. Pharmacological modulation of IM regulates the emergence and the frequency regime of both pacemaker and CPG activities, and controls the speed of locomotion. Computational models captured these results and show howed an interplay between IM and INaP that endows the locomotor CPG with rhythmogenic properties. Overall, this study provides fundamental insights into how IM and INaP work in tandem to set the speed of locomotion.

scholarly journals The critical role of persistent sodium current in hippocampal gamma oscillations

2020 ◽  
Vol 162 ◽  
pp. 107787
Author(s):  
Young-Jin Kang ◽  
Ethan M. Clement ◽  
Stefan L. Sumsky ◽  
Yangfei Xiang ◽  
In-Hyun Park ◽  
...  
Keyword(s):  
Sodium Current ◽  
Critical Role ◽  
Gamma Oscillations ◽  
Persistent Sodium Current

scholarly journals The M-current works in tandem with the persistent sodium current to set the speed of locomotion

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000738
Author(s):  
Jérémy Verneuil ◽  
Cécile Brocard ◽  
Virginie Trouplin ◽  
Laurent Villard ◽  
Julie Peyronnet-Roux ◽  
...  
Keyword(s):  
Computational Models ◽  
Sodium Current ◽  
Outward Current ◽  
Persistent Sodium Current ◽  
Pacemaker Neurons ◽  
Locomotor Rhythm ◽  
M Current ◽  
Frequency Regime ◽  
Locomotion Speed

The central pattern generator (CPG) for locomotion is a set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current (INaP). How they proceed to regulate the locomotor rhythm remained unknown. Here, in neonatal rodents, we identified a persistent potassium current critical in regulating pacemakers and locomotion speed. This current recapitulates features of the M-current (IM): a subthreshold noninactivating outward current blocked by 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) and enhanced by N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide (ICA73). Immunostaining and mutant mice highlight an important role of Kv7.2-containing channels in mediating IM. Pharmacological modulation of IM regulates the emergence and the frequency regime of both pacemaker and CPG activities and controls the speed of locomotion. Computational models captured these results and showed how an interplay between IM and INaP endows the locomotor CPG with rhythmogenic properties. Overall, this study provides fundamental insights into how IM and INaP work in tandem to set the speed of locomotion.

scholarly journals The Role of the Persistent Sodium Current in Epilepsy

2020 ◽  
pp. 153575972097397
Author(s):  
Eric R. Wengert ◽  
Manoj K. Patel
Keyword(s):  
Action Potentials ◽  
Cell Function ◽  
Sodium Current ◽  
Persistent Sodium Current ◽  
Sodium Ions ◽  
Pathogenic Role ◽  
The Past ◽  
Voltage Gated Sodium Channels ◽  
Total Sodium

Voltage-gated sodium channels (VGSCs) are foundational to excitable cell function: Their coordinated passage of sodium ions into the cell is critical for the generation and propagation of action potentials throughout the nervous system. The classical paradigm of action potential physiology states that sodium passes through the membrane only transiently (1-2 milliseconds), before the channels inactivate and cease to conduct sodium ions. However, in reality, a small fraction of the total sodium current (1%-2%) remains at steady state despite prolonged depolarization. While this persistent sodium current (INaP) contributes to normal physiological functioning of neurons, accumulating evidence indicates a particularly pathogenic role for an elevated INaP in epilepsy (reviewed previously 1 ). Due to significant advances over the past decade of epilepsy research concerning the importance of INaP in sodium channelopathies, this review seeks to summarize recent evidence and highlight promising novel anti-seizure medication strategies through preferentially targeting INaP.

Essential role of Sharpin in TNFα dependent NFκB activation in primary hepatocytes

2012 ◽  
Vol 50 (01) ◽  
Author(s):  
N Lange ◽  
S Sieber ◽  
A Erhardt ◽  
G Sass ◽  
HJ Kreienkamp ◽  
...  
Keyword(s):  
Essential Role ◽  
Primary Hepatocytes

Different Abilities of Thrombin Receptor Activating Peptide and Thrombin to Induce Platelet Calcium Rise and Full Release Reaction

1995 ◽  
Vol 74 (05) ◽  
pp. 1323-1328 ◽  
Author(s):  
Dominique Lasne ◽  
José Donato ◽  
Hervé Falet ◽  
Francine Rendu
Keyword(s):  
Essential Role ◽  
Calcium Influx ◽  
Dense Granule ◽  
Receptor Interaction ◽  
Thrombin Receptor ◽  
Release Reaction ◽  
External Calcium ◽  
Maximum Rise ◽  
Granule Release

SummarySynthetic peptides (TRAP or Thrombin Receptor Activating Peptide) corresponding to at least the first five aminoacids of the new N-terminal tail generated after thrombin proteolysis of its receptor are effective to mimic thrombin. We have studied two different TRAPs (SFLLR, and SFLLRN) in their effectiveness to induce the different platelet responses in comparison with thrombin. Using Indo-1/AM- labelled platelets, the maximum rise in cytoplasmic ionized calcium was lower with TRAPs than with thrombin. At threshold concentrations allowing maximal aggregation (50 μM SFLLR, 5 μM SFLLRN and 1 nM thrombin) the TRAPs-induced release reaction was about the same level as with thrombin, except when external calcium was removed by addition of 1 mM EDTA. In these conditions, the dense granule release induced by TRAPs was reduced by over 60%, that of lysosome release by 75%, compared to only 15% of reduction in the presence of thrombin. Thus calcium influx was more important for TRAPs-induced release than for thrombin-induced release. At strong concentrations giving maximal aggregation and release in the absence of secondary mediators (by pretreatment with ADP scavengers plus aspirin), SFLLRN mobilized less calcium, with a fast return towards the basal level and induced smaller lysosome release than did thrombin. The results further demonstrate the essential role of external calcium in triggering sustained and full platelet responses, and emphasize the major difference between TRAP and thrombin in mobilizing [Ca2+]j. Thus, apart from the proteolysis of the seven transmembrane receptor, another thrombin binding site or thrombin receptor interaction is required to obtain full and complete responses.

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Time Course ◽  
Essential Role ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
High Doses ◽  
Induced Aggregation

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

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