Sodium ion channels

Catterall,W.A., Goldin,A. L. andWaxman, S. G. International Union of Pharmacology. XXXIX. Compendium of voltagegated ion channels sodium channels. Pharmacol. Rev. 55 575-578, 2003. 

Catterall WA, Goldin AL, Waxman SG Compendium of voltage-gated ion channels Sodium channels. Pharmacol Rev 2003 55 575. [PMID 14657413]... 

Information on the mechanism of action of gambierol is scarce. Recent pharmacological studies on this toxin led to clarification of its possible targets. Gambierol could be affecting two distinct voltagegated ion channels sodium and potassium. ... 

A subset of ion channels not gated by traditional neurotransmitters represents another receptor class. These iaclude potassium, calcium, sodium, and cychc adenosiae monophosphate (cAMP)-gated channels (14—16) for which a large number of synthetic molecules exist that alter ceUular function. 

Local anesthetics produce anesthesia by blocking nerve impulse conduction in sensory, as well as motor nerve, fibers. Nerve impulses are initiated by membrane depolarization, effected by the opening of a sodium ion channel and an influx of sodium ions. Local anesthetics act by inhibiting the channel s opening they bind to a receptor located in the channel s interior. The degree of blockage on an isolated nerve depends not only on the amount of dmg, but also on the rate of nerve stimulation (153—156). 

Kellenberger S, Schild L (2002) Epithelial sodium channel/degenerin family of ion channels a variety of functions for a shared structure. Physiol Rev 82 735-767... 

Besides sodium channels, other ion channels such calcium- and potassium channels as well as certain ligand-gated channels are affected by local anaesthetics. However, this plays only a minor role for nerve block but may have more impact on adverse effects induced by systemical concentrations of these drags. 

Neurotransmitter transport can be electrogenic if it results in the net translocation of electrical charge (e.g. if more cations than anions are transferred into the cell interior). Moreover, some transporters may direction-ally conduct ions in a manner akin to ligand-gated ion channels this ion flux is not coupled to substrate transport and requires a separate permeation pathway associated with the transporter molecule. In the case of the monoamine transporters (DAT, NET, SERT) the sodium current triggered by amphetamine, a monoamine and psychostimulant (see Fig. 4) is considered responsible for a high internal sodium concentration... 

Sensory receptors expressed in particular in taste receptor cells of the taste buds that sense the five basic tastes salt, sour, sweet, bitter and umami (glutamate taste). Sodium type ion channels sense salty taste whereas sour taste is transduced by potassium type ion channels. The underlying cause of sweet, bitter, and umami tastes is the selective activation of different groups of G protein coupled receptors that discriminate between sweet, bitter, and umami tasting molecules. 

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... 

In the Long QT Syndrome (LQTS), the repolarization phase of the cardiac muscle is delayed, rendering the heart vulnerable to an arrhythmia known as torsade de pointes. LQTS is associated with five genes encoding ion channels. LQTS type 3 (LQT3) results from mutations of Nav1.5, which cause persistent sodium cunent. In contrast, sodium channel mutations associated with Biugada syndrome reduce the expression level of cardiac sodium channels. 

Over 40 different types of polypeptide toxins have been found in marine animals (i). Many of these toxins are exquisitely selective in their actions, affecting a single process or receptor at minute concentrations. So far the sea anemone and gastropod Conus) toxins have attracted the most attention as molecular probes of ion channels. In this chapter, we discuss several approaches which are being used to investigate, at the molecular level, the interactions of the sea anemone neurotoxic polypeptides with sodium channels. 

Birch and coworkers studied the time-intensity interrelationships for the sweetness of sucrose and thaumatin, and proposed three thematically different processes (see Fig. 47). In mechanism (1), the sweet stimuli approach the ion-channel, triggering site on the taste-cell membrane, where they bind, open the ion-channel (ionophore), and cause a flow of sodium and potassium ions into, or out of, the cell. Such a mechanism would correspond to a single molecular event, and would thus account for both time and intensity of response, the intensity of response being dependent on the ion flux achieved while the stimulus molecule binds to the ionophore. 

Hydrogen ions accumulate in tissue damaged by inflammation and ischaemia and so pH is lowered. These protons may activate nociceptors directly via their own family of ion channels as well as sensitising them to mechanical stimulation. Acid-sensing ion channels (ASICS) are a family of sodium channels that are activated by protons — of special interest is one type found only in small dorsal root ganglion neurons that possibly are responsible for activation of nociceptors. Although the transduction of mechanical stimuli is poorly understood, ASICs are closely related to channels that respond to stretch. 

As with the biosynthesis of anandamide, the biosynthesis of 2-AG is also triggered by increases of intracellular calcium ions that result from neuronal activity. High frequency stimulation of neurons produced a fourfold increase of 2-AG accumulation compared with controls, and this was prevented by sodium ion channel blocking or removal of calcium ions (Stella, 1997). The concentration of 2-AG in depolarized neurons reached 1 to 2 pM, significantly higher than anandamide and sufficient to substantially activate CB1 (Stella, 1997). 

The ion-channel blocking mechanism has been widely tested and found to be important in both pharmacology and physiology. Examples are the block of nerve and cardiac sodium channels by local anesthetics, or block of NMDA receptor channels by Mg2+ and the anesthetic ketamine. The channel-block mechanism was first used quantitatively to describe block of the squid axon K+ current by tetraethylammonium (TEA) ions. The effects of channel blockers on synaptic potentials and synaptic currents were investigated, particularly at the neuromuscular junction, and the development of the single-channel recording technique allowed channel blockages to be observed directly for the first time. 

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. 

Rapid-acting neurotoxin that inhibits sodium-ion channels in neural and muscular tissue. It does not affect the neuromuscular junction. It is colorless crystals or a white powder that is obtained from puffer fish (Arothron sp.), frogs, newts, dinoflagellates (Takifugu poecilonotus), and bacteria (Pseudoalteromonas tetraodonis). It is heat stable but darkens on heating above... 

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. 

Barchi, R. L. Voltage-sensitive sodium ion channels. Molecular properties and functional reconstitution. Trends Biochem. Sci. 9, 358-361,1984. 

The amiloride-sensitive FMRF-amide-gated sodium ion channel is among the few peptide-gated ion channels identified 328 Neuropeptide receptors are becoming molecular targets for therapeutic drugs 328... 

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