Voltage sodium channels

Catterall, WA. 2000. From ionic currents to molecular mechanisms The structure and function of voltaged sodium channels. Neuron 26, 13-25. 

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. 

Electrophysiological studies (mainly using voltage-clamp and patch clamp) revealed the essential properties of the sodium channels kinetics of channel gating and selective ion permeation. Sodium channels are... 

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... 

Catterall WA, Goldin AL, Waxman SG (2005) International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 57 397-409. 

The saxitoxins function by binding to a site on the extracellular surface of the voltage-activated sodium channel, interrupting the passive inward flux of sodium ions that would normally occur through the channel while it is in a conducting... 

Brevetoxins Unique Activators of Voltage-Sensitive Sodium Channels... 

Research in this area advanced in the 1970 s as several groups reported the isolation of potent toxins from P. brevis cell cultures (2-7). To date, the structures of at least eight active neurotoxins have been elucidated (PbTx-1 through PbTx-8) (8). Early studies of toxic fractions indicated diverse pathophysiological effects in vivo as well as in a number of nerve and muscle tissue preparations (reviewed in 9-11). The site of action of two major brevetoxins, PbTx-2 and PbTx-3, has been shown to be the voltage-sensitive sodium channel (8,12). These compounds bind to a specific receptor site on the channel complex where they cause persistent activation, increased Na flux, and subsequent depolarization of excitable cells at resting... 

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. 

DDT enters an insect by dissolving the thin layer of fatty substances that repel water from the creature s waxy outer skin. Penetrating the layer, DDT reaches the insect s nerve endings and gradually paralyzes vital nerve centers. After a short period of extraordinary excitement, insects sprayed with DDT become progressively paralyzed, fall on their backs, and die. Later, it was learned that DDT allows sodium ions to enter insect tissue through voltage-sensitive channels and make the nerves fire uncontrollably. Because animals and people absorb much less sodium in their tissues, DDT is selectively toxic to insects. 

Schultz, J., Hoffmuller, U., Krause, G., Ashurst, J., Macias, M. J., Schmieder, P., Schneider-Mergener, J., and Oschknat, H. (1998). Specific interactions between the syntrophin PDZ domain and voltage-gated sodium channels. Nat. Struct. Biol. 5, 19-24. 

Understand the function of sodium and potassium voltage-gated channels... 

Sodium channels open more rapidly than K+ channels because they are more voltage sensitive and a small depolarization is sufficient to open them. Larger changes in membrane potential associated with further cell excitation are required to open the less voltage-sensitive K+ channels. Therefore, the increase in the permeability of K+ ions occurs later than that of Na+ ions. This is functionally significant because if both types of ion channels opened concurrently, the change in membrane potential that would occur due to Na+ ion influx would be cancelled out by K+ ion efflux and the action potential could not be generated. 

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