Channel, sodium channels, voltage-dependent

Tetrodotoxin Bacteria Alkaloid (guanidine) Inhibitor of sodium channels, voltage-dependent 385/1 mg... 

The second class of channels are the voltage-dependent sodium channels, where histrionicotoxins reduce conductances in a manner reminiscent of local anesthetics (61). The third class are the voltage-dependent potassium channels, where histrionicotoxins reduce conductances in a time- and stimulus-dependent manner. Structure-activity relationships for histrionicotoxins differ at the three classes of channels (61). 

The pharmacological activity of decahydroquinoline ci5-195A and analogs in neuromuscular preparations appears to involve noncompetitive blockade both of nicotinic receptor-channels and of voltage-dependent sodium and potassium channels (see reviews in Refs. 3 and 5). Recently, both cis- and rra/i5-decahydroquinolines were shown to block ion flux through nicotinic receptor channels in pheochromocytoma cells and to enhance the rate of desensitization of such nicotinic channels (64,82). 

Voltage-dependent sodium channels are a family of membrane proteins that mediate rapid Na+ influx, in response to membrane depolarization to generate action potentials in excitable cells. 

Molecularly, mammalian voltage-dependent sodium channels are composed of the main pore forming a subunit and smaller auxiliary (3 subunits. The rat brain sodium channel contains the 260-kD a subunit, the 36-kD (31 subunit and the 33-kD (32 subunit. The subunit stoichiometry is a (31 (32 = 1 1 1. 

Voltage-dependent Na Channels. Table 1 Mammalian sodium channel a subunits... 

Protozoa and Porifera. The pharmacology and toxicology of the dinoflagellate toxins which act upon the voltage- and time-dependent sodium channel found in nerves of vertebrates and invertebrates, and the skeletal muscle of vertebrates, are discussed in other chapters in this volume. 

In erythrocytes and most other cells, the major structural link of plasma membranes to the cytoskeleton is mediated by interactions between ankyrin and various integral membrane proteins, including Cf/HCOj antiporters, sodium ion pumps and voltage-dependent sodium ion channels. Ankyrin also binds to the =100 nm, rod-shaped, antiparallel a(3 heterodimers of spectrin and thus secures the cytoskeleton to the plasma membrane. Spectrin dimers self-associate to form tetramers and further to form a polygonal network parallel to the plasma membrane (Fig. 2-9D). Neurons contain both spectrin I, also termed erythroid spectrin, and spectrin II, also termed fodrin. Spectrin II is found throughout neurons, including axons, and binds to microtubules, whereas spectrin I occurs only in the soma and dendrites. 

Lamotrigine blocks voltage-dependent sodium channels and inhibits high-voltage activated Ca channels. 

Phenytoin inhibits voltage-dependent sodium channels. 

Topiramate affects voltage-dependent sodium channels, GABA receptors, high voltage Ca channels, and kainate a-amino-3-hydroxy-5-methylisox-azole-4-propionic acid subunits. 

Zonisamide is a broad-spectrum sulfonamide AED that blocks voltage-sensitive sodium channels by reducing voltage-dependent T-type Ca channels it also weakly inhibits carbonic anhydrase, and inhibits glutamate release. 

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