Ion channel disorders

Ptacek, L. J. Channelopathies ion channel disorders of muscle as a paradigm for paroxysmal disorders of the nervous system. Neuromusc. Disord. 7 250-255,1997. 

Bulman DE 1997 Phenotype variation and newcomers in ion channel disorders. Hum Mol Genet 6 1679-1685... 

An important characteristic of both classes of ion channel is that they possess multiple dmg binding sites (Table 2). Many of the channel-active dmgs have achieved particular therapeutic importance, including, for example, the Ca " antagonists, widely used for a number of cardiovascular disorders. 

The disorders listed are discussed further in other chapters. The table lists examples of mutations affecting receptors, a transporter, an ion channel, an enzyme, and a structural protein. Examples of altered or defective glycosylation of glycoproteins are also presented. Most of the conditions listed affect the plasma membrane. 

Felix R Channelopathies ion channel defects linked to heritable clinical disorders. J Med Genet 2000 37 729. 

Table 49-5. Some disorders (channelopathies) due to mutations in genes encoding polypeptide constituents of ion channels. ...

Andreoli TE Ion transport disorders introductory comments. Am J Med 1998 104 85. (First of a series of articles on ion transport disorders published between January and August, 1998. Topics covered were structure and function of ion channels, arrhythmias and antiarrhythmic drugs, Liddle syndrome, cholera, malignant hyperthermia, cystic fibrosis, the periodic paralyses and Bartter syndrome, and Gittelman syndrome.)... 

Mechanism of Action The mechanism of action of lamotrigine appears to involve blockage of ion channels and effects on glutamate transmission, although the precise mechanism in bipolar disorder is not clear.33... 

Narahashi T Northwestern University Medical School, Chicago, IL The effects of therapeutic drugs and toxins on neuronal ion channels National Institute of Neurological Disorders and Stroke... 

The epilepsies constitute a common, serious neurological disorder in humans, affecting approximately 60 million people worldwide. Well in excess of 40 distinct epileptic syndromes have been identified to date. Current treatment is only symptomatic except in uncommon instances when surgical treatment is possible. While available antiseizure medications target ion channels such as the y-amino-butyric acid (GABA)a receptor and voltage activated sodium (Na+) channels, current research seeks to elucidate the cellular and molecular mechanisms by which a normal brain becomes epileptic. Hopefully, this research will lead to the identification of new targets for which small molecules can be identified and used for prevention or cure of epilepsy. 

Alcoholism is a chronic relapsing disorder 922 Ethanol interacts directly with ligand-gated and voltage-gated ion channels 922... 

One model of an ionic mechanism of action of Li+ in affective disorders has been proposed, in which the receptors for Li+ are ion channels and cation coenzyme receptor sites, and in which the presence of intracellular Li+ in excitable cells results in the displacement of exogenous Na+ and/or other intracellular cations [13]. It has been suggested that this could lead to a decrease in the release of neurotransmitters alternatively it may be that this intracellular Li+ is altering a preexisting, disease-related electrolyte imbalance [14]. A number of observations of such imbalances in affective disorders have been made depression is associated with elevated levels of intracellular Na+ [15] retention of Li+ is observed in manic-depressive patients prior to an episode of mania [ 16] and Na+/K+ activity is defective during both mania and depression [17]. 

Luginger E, Wenning GK, BOsch S, Poewe W (2000) Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson s disease. Mov Disord 15 873-878 Ly CD, Roche KW, Lee HK, Wenthold RJ (2002) Identification of rat EMAP, a delta-glutamate receptor binding protein. Biochem Biophys Res Commun 291 85-90 Madden DR (2002) The structure and function of glutamate receptor ion channels. Nat Rev Neurosci 3 91-101... 

Depue RA, Arbisi P, Spoont MR, et al Dopamine functioning in the behavioural facilitation system and seasonal variation in behaviour normal populations and clinical studies, in Seasonal Affective Disorders and Phototherapy. Edited by Rosenthal NE, Blehar MC. New York, Guilford, 1989, pp 230-259 Derkach V, Surprenant A, North RA 5-E1T3 receptors are membrane ion channels. Nature 339 706-709, 1989... 

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