scholarly journals Molecular identification and functional role of voltage-gated sodium channels in rat carotid body chemoreceptor cells. Regulation of expression by chronic hypoxia in vivo

2007 ◽  
Vol 102 (1) ◽  
pp. 231-245 ◽  
Author(s):  
Ana I. Caceres ◽  
Ana Obeso ◽  
Constancio Gonzalez ◽  
Asuncion Rocher
Keyword(s):  
Sodium Channels ◽  
Molecular Identification ◽  
Carotid Body ◽  
Functional Role ◽  
Chronic Hypoxia ◽  
Regulation Of Expression ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Interpreting the functional role of a novel interaction motif in prokaryotic sodium channels

2017 ◽  
Vol 149 (6) ◽  
pp. 613-622 ◽  
Author(s):  
Altin Sula ◽  
B.A. Wallace
Keyword(s):  
Sodium Channels ◽  
Functional Role ◽  
Structural Features ◽  
Channel Activation ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Channel Opening ◽  
Activated State ◽  
Electrical Signaling

Voltage-gated sodium channels enable the translocation of sodium ions across cell membranes and play crucial roles in electrical signaling by initiating the action potential. In humans, mutations in sodium channels give rise to several neurological and cardiovascular diseases, and hence they are targets for pharmaceutical drug developments. Prokaryotic sodium channel crystal structures have provided detailed views of sodium channels, which by homology have suggested potentially important functionally related structural features in human sodium channels. A new crystal structure of a full-length prokaryotic channel, NavMs, in a conformation we proposed to represent the open, activated state, has revealed a novel interaction motif associated with channel opening. This motif is associated with disease when mutated in human sodium channels and plays an important and dynamic role in our new model for channel activation.

scholarly journals Mining the Virgin Land of Neurotoxicology: A Novel Paradigm of Neurotoxic Peptides Action on Glycosylated Voltage-Gated Sodium Channels

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Zhirui Liu ◽  
Jie Tao ◽  
Pin Ye ◽  
Yonghua Ji
Keyword(s):  
Sodium Channels ◽  
Network Activity ◽  
Voltage Gated ◽  
Virgin Land ◽  
Neuronal Network Activity ◽  
Voltage Gated Sodium Channels ◽  
Pharmacological Targets ◽  
Underlying Mechanisms ◽  
Posttranslation Modification

Voltage-gated sodium channels (VGSCs) are important membrane protein carrying on the molecular basis for action potentials (AP) in neuronal firings. Even though the structure-function studies were the most pursued spots, the posttranslation modification processes, such as glycosylation, phosphorylation, and alternative splicing associating with channel functions captured less eyesights. The accumulative research suggested an interaction between the sialic acids chains and ion-permeable pores, giving rise to subtle but significant impacts on channel gating. Sodium channel-specific neurotoxic toxins, a family of long-chain polypeptides originated from venomous animals, are found to potentially share the binding sites adjacent to glycosylated region on VGSCs. Thus, an interaction between toxin and glycosylated VGSC might hopefully join the campaign to approach the role of glycosylation in modulating VGSCs-involved neuronal network activity. This paper will cover the state-of-the-art advances of researches on glycosylation-mediated VGSCs function and the possible underlying mechanisms of interactions between toxin and glycosylated VGSCs, which may therefore, fulfill the knowledge in identifying the pharmacological targets and therapeutic values of VGSCs.

The Role of Nonprotein Domains in the Function and Synthesis of Voltage-Gated Sodium Channels

Ion Channels ◽  
1990 ◽  
pp. 33-64 ◽  
Author(s):  
S. R. Levinson ◽  
W. B. Thornhill ◽  
D. S. Duch ◽  
E. Recio-Pinto ◽  
B. W. Urban
Keyword(s):  
Sodium Channels ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Sodium Channel Nav1.3 Is Expressed by Polymorphonuclear Neutrophils during Mouse Heart and Kidney Ischemia InVivo and Regulates Adhesion, Transmigration, and Chemotaxis of Human and Mouse Neutrophils In Vitro

2018 ◽  
Vol 128 (6) ◽  
pp. 1151-1166 ◽  
Author(s):  
Marit Poffers ◽  
Nathalie Bühne ◽  
Christine Herzog ◽  
Anja Thorenz ◽  
Rongjun Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Polymorphonuclear Neutrophils ◽  
Human Neutrophils ◽  
Mouse Heart ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

Abstract Background Voltage-gated sodium channels generate action potentials in excitable cells, but they have also been attributed noncanonical roles in nonexcitable cells. We hypothesize that voltage-gated sodium channels play a functional role during extravasation of neutrophils. Methods Expression of voltage-gated sodium channels was analyzed by polymerase chain reaction. Distribution of Nav1.3 was determined by immunofluorescence and flow cytometry in mouse models of ischemic heart and kidney injury. Adhesion, transmigration, and chemotaxis of neutrophils to endothelial cells and collagen were investigated with voltage-gated sodium channel inhibitors and lidocaine in vitro. Sodium currents were examined with a whole cell patch clamp. Results Mouse and human neutrophils express multiple voltage-gated sodium channels. Only Nav1.3 was detected in neutrophils recruited to ischemic mouse heart (25 ± 7%, n = 14) and kidney (19 ± 2%, n = 6) in vivo. Endothelial adhesion of mouse neutrophils was reduced by tetrodotoxin (56 ± 9%, unselective Nav-inhibitor), ICA121431 (53 ± 10%), and Pterinotoxin-2 (55 ± 9%; preferential inhibitors of Nav1.3, n = 10). Tetrodotoxin (56 ± 19%), ICA121431 (62 ± 22%), and Pterinotoxin-2 (59 ± 22%) reduced transmigration of human neutrophils through endothelial cells, and also prevented chemotactic migration (n = 60, 3 × 20 cells). Lidocaine reduced neutrophil adhesion to 60 ± 9% (n = 10) and transmigration to 54 ± 8% (n = 9). The effect of lidocaine was not increased by ICA121431 or Pterinotoxin-2. Conclusions Nav1.3 is expressed in neutrophils in vivo; regulates attachment, transmigration, and chemotaxis in vitro; and may serve as a relevant target for antiinflammatory effects of lidocaine.

scholarly journals Targeted Osmotic Lysis of Highly Invasive Breast Carcinomas Using Pulsed Magnetic Field Stimulation of Voltage-Gated Sodium Channels and Pharmacological Blockade of Sodium Pumps

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1420
Author(s):  
Dennis Paul ◽  
Paul Maggi ◽  
Fabio Del Piero ◽  
Steven D. Scahill ◽  
Kelly Jean Sherman ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Electrical Current ◽  
Normal Breast ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Reduce Tumor Growth ◽  
Osmotic Lysis ◽  
Stimulation Of

Concurrent activation of voltage-gated sodium channels (VGSCs) and blockade of Na+ pumps causes a targeted osmotic lysis (TOL) of carcinomas that over-express the VGSCs. Unfortunately, electrical current bypasses tumors or tumor sections because of the variable resistance of the extracellular microenvironment. This study assesses pulsed magnetic fields (PMFs) as a potential source for activating VGSCs to initiate TOL in vitro and in vivo as PMFs are unaffected by nonconductive tissues. In vitro, PMFs (0–80 mT, 10 msec pulses, 15 pps for 10 min) combined with digoxin-lysed (500 nM) MDA-MB-231 breast cancer cells stimulus-dependently. Untreated, stimulation-only, and digoxin-only control cells did not lyse. MCF-10a normal breast cells were also unaffected. MDA-MB-231 cells did not lyse in a Na+-free buffer. In vivo, 30 min of PMF stimulation of MDA-MB-231 xenografts in J/Nu mice or 4T1 homografts in BALB/c mice, concurrently treated with 7 mg/kg digoxin reduced tumor size by 60–100%. Kidney, spleen, skin and muscle from these animals were unaffected. Stimulation-only and digoxin-only controls were similar to untreated tumors. BALB/C mice with 4T1 homografts survived significantly longer than mice in the three control groups. The data presented is evidence that the PMFs to activate VGSCs in TOL provide sufficient energy to lyse highly malignant cells in vitro and to reduce tumor growth of highly malignant grafts and improve host survival in vivo, thus supporting targeted osmotic lysis of cancer as a possible method for treating late-stage carcinomas without compromising noncancerous tissues.

scholarly journals The Emerging Role of Voltage-Gated Sodium Channels in Tumor Biology

2019 ◽  
Vol 9 ◽  
Author(s):  
Weijia Mao ◽  
Jie Zhang ◽  
Heinrich Körner ◽  
Yong Jiang ◽  
Songcheng Ying
Keyword(s):  
Sodium Channels ◽  
Tumor Biology ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals In vivo potency of different ligands on voltage-gated sodium channels

2015 ◽  
Vol 762 ◽  
pp. 158-164 ◽  
Author(s):  
Arpad Safrany-Fark ◽  
Zita Petrovszki ◽  
Gabriella Kekesi ◽  
Peter Liszli ◽  
Gyorgy Benedek ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Axons provide the secretory machinery for trafficking of voltage-gated sodium channels in peripheral nerve

2016 ◽  
Vol 113 (7) ◽  
pp. 1823-1828 ◽  
Author(s):  
Carolina González ◽  
José Cánovas ◽  
Javiera Fresno ◽  
Eduardo Couve ◽  
Felipe A. Court ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Neural Function ◽  
Axonal Membrane ◽  
Local Synthesis ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

The regulation of the axonal proteome is key to generate and maintain neural function. Fast and slow axoplasmic waves have been known for decades, but alternative mechanisms to control the abundance of axonal proteins based on local synthesis have also been identified. The presence of the endoplasmic reticulum has been documented in peripheral axons, but it is still unknown whether this localized organelle participates in the delivery of axonal membrane proteins. Voltage-gated sodium channels are responsible for action potentials and are mostly concentrated in the axon initial segment and nodes of Ranvier. Despite their fundamental role, little is known about the intracellular trafficking mechanisms that govern their availability in mature axons. Here we describe the secretory machinery in axons and its contribution to plasma membrane delivery of sodium channels. The distribution of axonal secretory components was evaluated in axons of the sciatic nerve and in spinal nerve axons after in vivo electroporation. Intracellular protein trafficking was pharmacologically blocked in vivo and in vitro. Axonal voltage-gated sodium channel mRNA and local trafficking were examined by RT-PCR and a retention-release methodology. We demonstrate that mature axons contain components of the endoplasmic reticulum and other biosynthetic organelles. Axonal organelles and sodium channel localization are sensitive to local blockade of the endoplasmic reticulum to Golgi transport. More importantly, secretory organelles are capable of delivering sodium channels to the plasma membrane in isolated axons, demonstrating an intrinsic capacity of the axonal biosynthetic route in regulating the axonal proteome in mammalian axons.

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