Voltage-gated sodium channels are encoded by a family of ten structurally-related genes that are expressed in spatially and temporally distinct patterns, mainly in excitable tissues. They underlie electrical signalling in nerve and muscle. It has long been known that sodium channel blockers are anaesthetics as well as powerful analgesics when delivered at low concentrations. In addition, cardiac arrhythmias and epileptic activity can be treated with sodium channel blockers. As we have learned more about the sub-types of sodium channels and their distribution, new therapeutic opportunities have suggested themselves. There are indications that sodium channel blockers may also be useful in affective disorders and schizophrenia. The production of tissue-specific and eventually inducible knock out mice as well as genetic studies has proved useful in understanding the specialised role of individual types of sodium channels. The development of sub-type specific blockers has proved slower than anticipated, although the properties of naturally occurring toxin blockers suggest that subtype-specific blockers of sodium channels could be very useful clinically in the treatment of pain.
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http://dx.doi.org/10.2174/1568026054367584 | DOI Listing |
J Neurosci
January 2025
Carney Institute for Brain Science, Brown University, Providence, RI 02912
The neuromuscular junction (NMJ) is the linchpin of nerve-evoked muscle contraction. Broadly, the function of the NMJ is to transduce nerve action potentials into muscle fiber action potentials (MFAPs). Efficient neuromuscular transmission requires both cholinergic signaling, responsible for generation of endplate potentials (EPPs), and excitation, the amplification of the EPP by postsynaptic voltage-gated sodium channels (Nav1.
View Article and Find Full Text PDFJ Neurosci
January 2025
Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada
Action potentials (spikes) are regenerated at each node of Ranvier during saltatory transmission along a myelinated axon. The high density of voltage-gated sodium channels required by nodes to reliably transmit spikes increases the risk of ectopic spike generation in the axon. Here we show that ectopic spiking is avoided because K1 channels prevent nodes from responding to slow depolarization; instead, axons respond selectively to rapid depolarization because K1 channels implement a high-pass filter.
View Article and Find Full Text PDFFront Nutr
January 2025
Nutrition Institute, Ljubljana, Slovenia.
Objective: Bakery products are considered as one of main dietary sources of sodium/salt in Slovenia. Our main objective was to assess the salt content in bread in Slovenia, focusing into different bread categories and sales channels. The data collected in 2022 was compared with year 2012.
View Article and Find Full Text PDFArch Pediatr
January 2025
CMR Neuromusculaire, Service de génétique médicale, Hôpital Estaing, CHU de Clermont-Ferrand, Clermont-Ferrand, France. Electronic address:
Background: Myotonia is the main feature of both myotonic dystrophy (DM) and non-dystrophic myotonia (NDM). It is felt as stiffness, pain, fatigue, and weakness. In France, mexiletine, a non-selective voltage-gated sodium channel blocker, is approved for the treatment of myotonia in adults with NDM, and it has a temporary recommendation for use in the symptomatic treatment of DM in adults.
View Article and Find Full Text PDFExp Appl Acarol
January 2025
Faculty of Science, Department of Molecular Biology and Genetics, Mugla Sıtkı Koçman University, Mugla, Türkiye.
The Varroa destructor (hereafter referred to as Varroa) is a major pest of honeybees that is generally controlled using pyrethroid-based acaricides. However, resistance to these insecticides has become a growing problem, driven by the acquisition of knockdown resistance (kdr) mutations in the mite's voltage-gated sodium channel (vgsc) gene. Resistance mutations in the vgsc gene, such as the L925V mutation, can confer resistance to pyrethroids like flumethrin and tau-fluvalinate.
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