Oxidative Stress in the in vivo DMBA Rat Model of Breast Cancer: Suppression by a Voltage-gated Sodium Channel Inhibitor (RS100642)

2012 ◽  
pp. n/a-n/a ◽  
Author(s):  
Kadir Batcioglu ◽  
A. Burcin Uyumlu ◽  
Basri Satilmis ◽  
Battal Yildirim ◽  
Neslihan Yucel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Sodium Channel ◽  
Rat Model ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Cancer Suppression

scholarly journals In vivo optogenetic activation of Nav1.8+ cutaneous nociceptors and their responses to natural stimuli

2017 ◽  
Vol 117 (6) ◽  
pp. 2218-2223 ◽  
Author(s):  
Megan L. Uhelski ◽  
Daniel J. Bruce ◽  
Philippe Séguéla ◽  
George L. Wilcox ◽  
Donald A. Simone
Keyword(s):  
Sodium Channel ◽  
Blue Light ◽  
Functional Properties ◽  
Nerve Fibers ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Multiple Stimulus ◽  
C Fiber ◽  
Stimulus Modalities

Optogenetic methods that utilize expression of the light-sensitive protein channelrhodopsin-2 (ChR2) in neurons have enabled selective activation of specific subtypes or groups of neurons to determine their functions. Using a transgenic mouse model in which neurons natively expressing Nav1.8 (a tetrodotoxin-resistant voltage-gated sodium channel) also express the light-gated channel ChR2, we have been able to determine the functional properties of Nav1.8-expressing cutaneous nociceptors of the glabrous skin in vivo. Most (44 of 53) of the C-fiber nociceptors isolated from Nav1.8-ChR2+ mice were found to be responsive to blue (470 nm) light. Response characteristics, including conduction velocity and responses to mechanical stimuli, were comparable between nociceptors isolated from Nav1.8-ChR2+ and control mice. Interestingly, while none of the non–light-responsive C-fibers were sensitive to heat or cold, nearly all (77%) light-sensitive fibers were excited by mechanical and thermal stimuli, suggesting that Nav1.8 is predominantly expressed by C-fiber nociceptors that are responsive to multiple stimulus modalities. The ability to activate peripheral nociceptors with light provides a method of stimulation that is noninvasive, does not require mechanical interruption of the skin, and accesses receptive fields that might be difficult or impossible to stimulate with standard stimuli while allowing repeated stimulation without injuring the skin. NEW & NOTEWORTHY Transgenic mice that express the blue light-sensitive protein channelrhodopsin2 (ChR2) in nociceptive nerve fibers that contain voltage-gated sodium channel Nav1.8 were used to determine functional properties of these afferent fibers. Electrophysiological recordings in vivo revealed that most nociceptive fibers that possess Nav1.8 are C-fiber nociceptors that respond to multiple stimulus modalities. Furthermore, responses evoked by blue light stimulation were comparable to those elicited by noxious mechanical, heat, and cold stimuli.

scholarly journals Voltage-Gated Sodium Channel Phosphorylation at Ser571 Regulates Late Current, Arrhythmia, and Cardiac Function In Vivo

Circulation ◽  
2015 ◽  
Vol 132 (7) ◽  
pp. 567-577 ◽  
Author(s):  
Patric Glynn ◽  
Hassan Musa ◽  
Xiangqiong Wu ◽  
Sathya D. Unudurthi ◽  
Sean Little ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

Abstract P361: Reduced Cardiac Tmem65 In Mouse Hearts Results In Intercalated Disc Defects And Eventual Dilated Cardiomyopathy With Cardiac Fibrosis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Allen C Teng ◽  
Liyang Gu ◽  
Michelle Di Paola ◽  
Zachary Williams ◽  
Aaron Au ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Sodium Channel ◽  
Connexin 43 ◽  
Cardiac Fibrosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Physical Interaction ◽  
Intercalated Disc ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

The intercalated disc (ICD) is unique membrane structure that is indispensable to normal heart function. However, its structural organization is not well understood. Previously, we showed that the ICD-bound transmembrane protein 65 (Tmem65) was required for connexin 43 (Cx43) localization in cultured mouse neonatal cardiomyocytes. Here, we investigated the role of Tmem65 in ICD organization in vivo . A mouse model was established by injecting CD1 mouse pups (3-7 days after birth) with recombinant adeno-associated virus 9 (rAAV9) harboring Tmem65 (or scrambled) shRNA. Quantitative polymerase chain reaction (qPCR) and immunoblots confirmed greater than 85% reduction in Tmem65 expression (7.1±0.7% remained for Tmem65 proteins; 14.4±2.5% remained for Tmem65 transcripts, n =4) in mouse ventricles compared to control hearts. Tmem65 knockdown (KD) mice exhibited heart failure-like symptoms as early as 3 weeks post viral administration. Specifically, Tmem65 KD mice developed eccentric hypertrophic cardiomyopathy in 3 weeks and dilated cardiomyopathy with severe cardiac fibrosis in 7 weeks, as confirmed by H&E and Masson’s Trichrome staining. Echocardiography and electrocardiography, respectively, showed depressed hemodynamics (19.27±1.46ml/min for cardiac output in control hearts vs. 6.63±0.52ml/min for Tmem65 KD hearts, n =6) and impaired conduction, including prolonged PR (22.7±1.85ms in control hearts vs. 28.89±3.85ms in Tmem65 KD hearts, n≥8), QRS intervals (10.47±0.42ms in control hearts vs. 16.35±0.36ms in Tmem65 KD hearts, n≥8), and slowed heart rate (415±10bpm in control hearts vs. 347±16bpm in Tmem65 KD hearts, n≥8) in Tmem65 KD mouse hearts. Immunoprecipitation and super-resolution microscopy confirmed the physical interaction and localization between Tmem65 and voltage-gated sodium channel β subunit (β1) at the ICD and this interaction was evidently required for the establishment of perinexal nanodomains and voltage-gated sodium channel 1.5 (NaV1.5) localization to the ICD. Disrupting Tmem65 function, thus, impaired perinexal structure, reduced conduction velocity, and ultimately resulted in cardiomyopathy in vivo .

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